February, 1977 CANCER MORTALITY RATES AMD DRINKING WATER 'IN 346 COUNTIES OF THE OHIO RIVER VALLEY BASIN BY Joyce Salg Department of Epidemiology- University of North Carolina Purchase Order 5-03-4S23J Project Officer Leiand J. McCabe Water Quality Division Health Effects Research Laboratory Office of Research and Development U. S. Environmental'Protection Agency Cincinnati, Ohio 45263' ------- ABSTRACT JOYCE SALG. Cancer Mortality Rates and DrinkisjJ 5fat;er Cwolity in the Ohio River Valley Basin A series of unweighted and weighted regression analyses were used to dateraina if an ecological association exists between drinking water in 346 counties lying within the Ohio River Valley Basin and Cancer Mortality Rates of individual and grouped organ sitas. Using twenty year, (1950-1969) age-adjusted county cancer mortality rates, I960 census denographic data and ntinicipal public watar data (1963), tvo water variables were successively studied: percent surface water usage (percentage cf a county's population whose drinking water source was from a aajor or siinor river) and percent prechlorination (percentage of a county's population served whose Orinking water underwent prechlorination). Ecological association between colorectal and bladder cancer mortality rates and the water variables suggests further research employing these specific sites will be most productive for hypothesis testing. ------- r ’ ‘v’i ‘.J Cbjectives . 6 1IEW OFTi- L ATT2 . Ex er enta1 v! e ce ‘ C ic i Lca1 Carciic€enic ty. . . . . . . . . . . . . . . . . 20 Ed.e o1cEjca1 Evld.ence fo Cr a 1c Chen’ical CaI1C1rc8eri C1t7 . . . . . . . . . . . . 22 A Z ThCDS. ter a1s. .. 3 ... . . 14.Q P tc t S ace Water Jsa... • Pe ei ± ? c cr± at oi. .. 69 i . ct ssIc . S S 107 ------- LIST OF TABLES 1 Trihiogenated—methate Content of Various Munici a1 Water Supplies . 2 Trihalogenatad—nethana Content of Water from Water— Treatment Plant 3 Organoch3.orina Compounds in. Water from Sewage Treatment Plant 4 Regression CoeffIcients for Variable Representing ProportIon of Drinking Water from Mississippi 16 5 Results: Presence (*) or absence (NS) of Statistical Signi- ficance at 5% Level for the Variable Representing Proportion of Drinking Water from Mississippi River 26 6 Su .ry of Significant Results Bet ;een. Percent Surface Water Usage and SLte, Race, Sex—specific Cancer Mortality Rates, 1950—1969, in 346 Study Counties 7 Estimated Percent Surface Racer Usage Regression Coefficients and socIated p—values from Un.weigh ed and Weighted Regres- sion Analyses of White Males, White Females nd Site—specific Cancer Mortality Rates Versus Selected Dernographic Risk Factors for Malignant Neoplasn Mortality, 1950—1969, in 346 untIes 8 Estimated Percent Surface Water Usage Ragrassion Ccefficer.ts and Associated p—values from Unweighted and Weighted Regres- sion Analyses of Non—white Males and Non—white Females and Site—specific Cancer Mortality Rates Versus Selected Demo- graphic Risk Factors for Malignant Nsoplasm :.iortalitv. 1930— 1969, in 346 Study Counties 9 Estimated Percent Surface Water Usage Regression Coefficients and Associated p—values from Unweighted and Weighted ? nalysas of the Gastrointestinal and Urinary Tract Systems Cancer Mor- tality Rates Versus Selected Demcgraphic Risk Factors for Malignant Neoplasm Mortality, 1930—1969, n 346 Counties 52 10 Estimated Percent Surface Water Usage Regression Coefficients and Associated n—values from Unweighted and Rei2hted Analyses of the Gastrointestinal and Urinary Tract Systems Cancer Mor— tality Rates Versus Salectad Demogra hic Risk Factors for Malignant Nec?1as Mcrtali , 19 0—1969, in f 6 Ccunt .es ------- 11 sti ated Percent Surface Water Usage Regression Coefficants and Associated p—values fron Weighted na1yses (reduced nodal) of Selected Sex-race, Site—specific Cancer Mortality Rates Versus Selected Dertogreohic Risk Pactors for Malignant sec— plasm Mortality, 1950—1969, in 346 Counties 57 12 Unweightad and Weighted Regression analyses of Percent Sur- face Water Usage and Co binad Sites: Large Intestine and Ractun for All Race—sex Groups 59 13 Estimated Percent Surface Water Coefficients and p—values for Cancer Site by Race—sex for Weighted Regression Analyses (reduced Model) Including Lung Cancer Mortality as a Pra— dictor Variable 14 Zatinated Percent Surface Water Usage Coefficients with p— values fro WeIghted Regression Analysis Stratified by Popu— laticn for 346 Study Counties 63 15 Zsti atad Percent Surface Water Coefficients with —va1ues from Wei htad Regression Analyses Stratified by Population for Counties with 0 Percent or More nown Water Source 66 16 Su arv of Significant Results Zetween Percent Prechloronation and Site—, Race—, and Sex—s ecific Cancer Mortality Rates. 1950—1969, in 346 Study Counties 71 17 Estinated Percent ?ra lorinacion Regression Cceffici3nts and Associated p—values fron Un eightad and Weighted Ragrassicn Analyses of White Males and White Fetialas and Site—s ecific Cancer MortalIty Rates Versus Selected Darograohic Risk Fac- tors for Ma1i ant Neo 1asn MortalIty, 1950—1969, in 346 Counties 72 18 Estinatad Percent Prechlorination Ragression Ccefficianrs and Associated a—values fron t.Tnweighted and Weighted Regression Analyses for Non—white Males and on— rhi:e Pansies and Sits— specific Cancer Mortality Rates Versus Selected Denograhic P sk Factors for Malignant Neoplasn Mortality, 1950—1969, in 346 Counties 19 Zstj ated Percent ?rachlorina:ion Regression Coefficients and Associated —va1ues fron Weighted Analyses (reduced nodal) of Selected Sex—race, Sita—s ecific Cancer Mortality Razes 7arsk.s Selected Denogra hic Risk Factors for Malignant Nec?lasn Mar- taiitv, 1950—1969, in 346 Counties 20 Unei htad and Wei hted Regression Analyses of Percent Pre— chlorination and Can ined Sites: Large Intestine and Ract for All Race—sex G:cu:s ------- 21 Estimated Percent Prachiorination Coefficients and p—values for Cancer Site by Race—sex for Weighted Regression Analyses (reduced modal) Including Lung Cancer Mortality as a Predictor Variable 22 Estimated Percent ?rechlcrination Coaffic ents with p—values from Weighted Regression Analyses Stratified by Population for 346 Study Counties 23 Estimated Percent Prechiorination Coefficients with p—values from Weighted Regress cn Analyses Stratified by Population for Counties with 50 Percent or More Known. Water Source 85 24 Significant RegressIon CoefficIents nd p—values of Unweightad Regressi3n Analysis for Percent Surface Water Usage and Se- lected Soda—economic Variables Organ Site—specific for T hite Males, Malignant Taop1asm Mortality, 1950—1969, in 346 Study Counties 1C8 25 SIgnificant Regression Coefficients and p—values of Unweighted Ragressiou Analysis for Percent Surface Water Usage and Se- lected Sccio—economic Variables Organ Site—specific for tfliite Females, MalIgnant Neoplas Mortality, 1950—1969, in 346 Study Counties 109 26 Significant Regression CoeffIcients and p—values of Unt-zeighted Regression Analysis for Percent Surface Water Usage and Se— lected Socia—econonic Variables Organ Sice—specific for Non— white Males,. Malignant Neoplasm Mortality, 1950—1969, in 346 Study Counties 110 27 Significant Regression Coefficients and p—va1ue of Unwaightad Regression Analysis for Percent Surface Water Usage and Se— lected Socio—econonic Variables Organ Site—specific for Non— white Females, Malignant Neoplasm Mortality, 1950—1969, in 346 Study Counties 28 Significant Regression Coefficients and p—values of Weighted Regression Analysis for Percent Surface Water Usage and Se- lected Socio—econctic Variables, Organ Site—specific for White Males, Malignant Neoplasm Mortality, 1950—1969, in 346 Study Counties 112 29 Significant Regression CoeffIcients and p—values of WeIghted Regression Analysis for Percent Surface Water Usage and Se- lected Socic—economic Variables, Organ Sita—soecifi: for t hita Fenale.s, Malignant Neoolasn Mortality, 1950—1969, in 346 Study Counties ------- 30 Significant ?.egression Coefficients and p—values of Weighted Regression Analysis for Percar.t Surface Water Usage and Selected Sccio—econonic Variables, Organ Site—specific for Non—white Males, Malignant Naoolasci Mortality, 1930—1969, ±n 346 Study Counties 11 31 Significant Regression Coefficients and p—values of Weighted Regression Analysis or Percent Surface Water Usage and galeeted Socic—econo ic Variables, Organ Site—specific for Non—white Fer.ales, Malignant Neopla.sn Mortality, 1950-1969, in 346 Study Counties 115 32 Significant Regression Coefficients and p—values of Weighted Regression Analyses (reduced model) for Percent urfaca Water Usage and Selected Socio—econonic Variables, Organ Site— Soecific for Sa: -race Groups, Malignant Naoolasn Mortality, 1950—1969, In 346 Study Counties 110 33 Significant Percent Surface Water Usage Rearession Coef- ficients and p—values fron Weighted Regression nalvses (re- duced rnodal), Sex—race—sita—s?ecific Cancer Mortality Rates Versu: Selected Socio—econonic Variables Stratified by Po u— lation fcr Malignant Naoniasn Mortality, 1950—1969, in 346 Study Counties 117 34 Significant Regression Coefflolenta -id p—values of Unweighted Regression Analysis for Percent ?rechlorinatiort and Selected Soclo—econoric Variables, Organ Size—specific for White Males, Malignant eop1aan Moriality, 1950—1969, in 346 Study Counties 12C 35 Significant Coefficients and —va1uas of Unweightad Regression Analysis for Percent Prechiorination and Selected Scdic— econonic Variables, Organ Sita—s ecific for White Penales, Malignant Neoclean Mortality, 1950—1969, in 346 Study CountIes 36 SignifIcant Ragresslcn Cceff cients and p—values of Unwaighted Regression Ana1y is for Percent Prechlorination and S l cted Socio—econo ic Variables, Organ Site—specific for Non—white Males, Malignant Nao lasn Mortality, 1950—1969, in 346 Study Counties 37 Significant Coefficients and p—values of U.-eightad grassi:n Analysis for Percent Prechiorination and elacted Socic— econc c Variobles, Organ Si —scecifi: for ycn—white Fenales, Malianan: Neco1a n Mortality, 1930—15, in 346 S udv LCUI1C .CS ------- 2 IIT!ODUCTICN Chemical carcinogens in th environment have been Lndict d as the pni ary ca ise of the ajor!ty of human cance:s Hcwever, until recently, little attention ‘az directed to the possibility that carcinoqens in d:in cinq vater ay be causally related to human cancers Potentially harmful chemical agents which may be present in public water supplies include heavy metals, pesticides, and a variety of organic and inorganic che icais——aqants ‘nich nay be potential carcinogens. Urban and dc estic sewage and dustrial ias es discharging into water sources, atmospheric carcinogenic contaminants present in rain water, pesticides nd fertilizer residues conta.ned in agricultural runoff, and inorganic substances incorporated into the soil and leached into the ground-—all may pollute surface and ground raters. In additicn, the icrcbial and aquatic populaticn of both virgin and polluted streams contributes metabolic products (Gregcrmpoulaus, 19 L ) - lso, prducts of decomposition nay present new problems of contam aticn and chenical and biological reactions may form mc:e hazardous compounds. ------- 3 Consequently, there is a potential for ctan ation within the foreseeable future because of both the increased urbanization and industrialization and the conseqa ent qrsat increase in dszand placed on lakes, rivers and underground sservoirs ( ueper, 1960) Several studies have shown cheticals having carcinogenic ctantial present in river vater tostel et al ,.,1965; sites and ienan/972) and in finished unicipa.l drinking water epe: and. payne, 1963; ndeleaan and Suess, 1970: un c and Stanley,1975)_ Pollo7ing a 1972 nvircnzeutal rctacticn geacy study C! industrial pollutants of the Lover ississippi iiver in Louisiana, ti e .2.A. water Su?ply Research la o:atory, Cincinnati 4 Ohio identified 66 different chezicals in the drinking qatar of av Orleans. Shortly thereaftsr, the consuoption of nunicipal dninicinq iater in Louisiana counties as found to be pcsit ve17 associated iith over—all cancer nortalit7 in ‘ihite zales (Page and E rris, 197 ) Although the adequacy of tho statizticzl nethcds enployed and the validity o the hunan health inte prataticus drain frc this study ‘ie:a challenged Ta:cne and Gart, 1575), continued scientific investicaticus (3dlla:, 197 ; !ock 9 157n) established that the chlorination p:ccess as ccnnonj..y practiced can result in the fcration of a of chlorinated o cc.np.!——sc:e of .ch are : c cc s s:ac-ted c :cge s ------- WL h the continued. dccu entation of the chenical ccnta iuaticn of drinkir g water in the U_S. md the possible adverse hunan health effects of chernically polluted drinking iater, the U. 2. Congress responded.. The Safe Drinking ater ict (PLS3—523) was signed into 1a by the President in December 1975. Section 1Z 2 of the Ict charged that a conprehensive study of public water supplies and. drinking water sources be und.erta en by the nvironoental Protection Igency to deternine the nature and. extent of ccnta ination by carcinogenic substances. Continued. studies by the nviron ental otection Agency have since identified. organIc coopounds in the drinking watar snp lies in the U.S .. (1976). Also, in a survey of 80 selected cities, the National Organics 3econnaissancs Survey eazured. -the concentrations of six halogenated cc pounds in raw and unfinished. iater.. :n these studies, sc e ccnpotLnds, particularly chioroforn, were ubiquitous in unici;al drinking suppl±es.. Under l .boatory experinenta3. conditions these coupounds have denonstrated carcinogenic activity in ani a1s.. owever, several issues renaln unresolved.: whether these sane agents are carcI oqens for hunans; what doses are within ac e tabla units; the shapes d. para eterz c the dcse—res;crse curves; concentration levels; the effects of rolo: ed e:pcszre to 7er7 lc arounts; and wh the iatar supt l’ , as one of nany pc sihl ens ------- -S .s o: a y porta c 9.. this stud7 was ui de ta1ce to i.vestigat ibethe watar supply, as one of rnany possibla exposure sources, is ceoqraphically related to cancer oztality. Two çeneral objectives a d thei: corespondiq specific objectives are conz dered.. ------- S OS CTIV!s General Ob ctLves: To determine Lf exists betveen source of public To deterxine if exists between chlcxination of sti;plie s. an ecolcgicai. assoc.ia.tion cancer mortality rates and drinkinq water.. an ecological association cancen o:talit rates and public d.rin king vat er Specif±c Cbjectives: To deterxine if an ec loqica]. associaticn exists betvaen race—sex-site—specific age— adlusted cancer orta.lity rates, 1950—1969, and erce:t of a county’s pçpulation vhose public dninkinq water is frou nalor and minor rivers in 2 6 connties of seven contiguous states: IllInois, nd.iana, entuc y, Cbio, ?e nsyivania, ‘en:essee and ies-t 7i: inia. To dets:nine if an co1cqica1 asscciation e:ists bet-ieen : c —se te—z ecific age— ------- adjusted cancer aota lity rates, 1950e1 969, and percent of a county’s population whose public drinking nt*r undergoes pnchlorination teataent in 3fl counties of seven contiguous states: fllinois, Indiana, Kentucky . Ohio, Pennsylvania, Tennessee and Vest virqiuia. 7 ------- CEIPTfl TWO 32T237 07 Tfl Lzfln :u32 ------- 9 E3VIZi C ’ T2Z LII TU E The qnestion of the potential for conta inaticn of drinking iater scu ces with carcinogens was g ’ en i etu and direction consequent to the identification of €5 different chenical conpounds in the dninkinq wate: of 1e z Cricans y the Environnental Protection genc Water Stip ly ?esea:ch Laboratory, Cincinnati, Ohio in 197LL I nn ber of u;dat s no place the figure at 313 or ’anic co pcunds identified in the drin2 inq water in the C. . {L?.iL,1976) One class of organics, pol uciear aro ati: h7d:ccarbcns (?A ),imclndes many cheoicals that are !crc .in to be ca:cincqenic to anirnals and nay be carcinogenic to nan A:d lnan and Suess 197O) :evie ied carcinogenic and ncn-carcino enic P in the water en’,ircnnent with enphasis on 3,L —benzypyr2n (3P). 3, -3enzyprene, a hiqh2.’r potent carcinogen, is ubiguitous — tbough z viou ly thought to be forned only by in p1ete c ust±cn, evide cs points to the e oq nous foroation cf n niants . Thile thei: sciubility in p :e er i. T 7 lo , they O 7 be lubnl zod by such ta nas ns fe :;ente, or na ct : ise occ ir in ------- 10 solution associated with or absorbed into a variety of colloidal naterials or biota and thereby be transported through the water environ ,ne.nt.. PIEs have been fouxd in Lndustrial and municipal waste effluents and occur in the sedi2ent and biota of and surface waters. ith. the or absorption by actIvated carbon, processes do not remove P? Es; been found in d.o eztic water (fresh) groundwater contained icrograrn per liter of P1 . water has beer. as high as 0006 Waste effluents have ranged fron per liter of 3,L — enz pyrene soils, ground waters excepticn of filtration other water treat ent consequently PIEs have supplies. ncontaninated fron 0.0O i to 0010 Carcinogenic PIE in ground aicrcqrans ‘per liter. 0.5 to 7.5 nicrcqra (Indelua ,1970). wedquocd and Cooper {!ueper: 1960) , who studied sludge from sewage for pclynucrear aronatio hydrocarbons in !ngland, de:onst ted the presence anong various PIEs of two carcinogens, 2, —Ben:ypy:ane and 1,2 - Benzanthracene. They suspected the carcinogenic P H was introduced into the s vaqe through effluents discharged frog gas works, washings fron acadan roads and atncspheri soot ashed fron the air by rain. Euee: (19S 1,i960,1963) did e ;eri:ental studies ac 7atad carbon absorbate.s of :n and finished pollutsd with dtrial—cnica2. effl:ents. A Using water ------- 11 fraction of the a scrbates were ad inistar d to mica by ea s of cutaneous appicaticn, bcuta.eo s injection, and oral ad inis-tra .on_ Results shoved that carci oqenic chemicals ars released. into bodies of water zeniinq as sources of d. nkinq wz.ter for the gener 1 population. The data incr i inates not only absorbates of raw water, but also those of f nizhe water, and tbns ind c te that carcinogenic che icals penetrate the filters used fcr akin rai water actsniolcq.calIy safe fcr hunan ccnsunpticn This study raised the question of whether the: daily consurnption of d kinq water containing i nte a o ints of chenical car incqenic pollutants o e any years iqht play a direct pninar7 or contributary role in. the production of cancers of internal crq s asong the general pcpula-ticn Rook (197L ) , f oo an. an. a17Z3i3 of the chlorine, inferred that the or an.ohaljdes found in ater after chlorination were not introduced by chlorine, but n st have originated in the water u on chlorination.; thus water—borne hu ic :aterials in the iater supply ‘iere chetical pr curscrz of several tnihalogenated oetban.e s;ecies.. urtber ivestiqaticns ba e so cn that haJ..ogenatad cc c n.ds a:e p inced durin chic mn.ati:ii in. iatens cc ninc hun.ic or othe: o:oa:Lc tan.c s . C ie7er, :; i.e iat n— bcn:e h:n.ic eniai ien ve::L :a a2- cies, t .e c .Lc 1 ------- 12 nature of aquatic hu ic substances is not sufficiently established to say with csrta nty that hese structures are the o t pcrtant part c±pa tz the hlo et ane production reactions. This point is pivota’ to an increase understanding of these reactions (Chriztnan et al..,1 76) 3ellar et al . (197Lfl postulated the widespread production of chlorinated organic naterial due to the rnany organic cc pounds cc nonly found in natural and waste waters that ay react with free chlorine. Thus the extensive use of chlorine in water and sewage-treatn.ent processes, in household and co nercial laundering, in paper-pulp bleaching, and in related processes was i plica ted. Subsequently, Eellar found organochioride co:pcunds in tap ‘iater while raw river water, source of tue tap water, contained none or rnuch low-er concentrations of the crqauohalide. where the water source w low in total onqanics, i.e., well water, resulting concentrations of haloqenated products were low. where the water source ‘ias high in total orqan.ics, i.e., surface waters, the :9sult :g concentration of halogenated produ s were high (see table 1) - ------- Table 1. Trihaloge ated— atha e Content of Various unicipaJ. Water SupplIes Sampling Sites Raw Water Scurce Data Collected Concentration, ,igI1 Ch1arofo Bro o— dich loro— methane - Dibrono- chior — ethene 100* Surface 8—73 94.0 20.8 2.0 100* Surface 2—74 • 37.3 . 9.1 1.3 101 Surface 2—74 70.3 10.2 Q,4** l02 Surface 2—74 152.0 6.2 Q,9** 103 Surface 2—74 4.0 2.9 <0.1 1Q4* Well 8—73 2.9 104* Well 2—74 4.4 1.9 0.9 105* Well 2—74 1.7 1.1 0.8* 106’ Well 12—73 3.5 from Bellar et al., 1974. * Sam 1e age <4 hours Sa 1e age unknc :; > 24 hours A;prox. value + 20 ?etceflt § o data ------- Similar resultz were round in exaaination of chlorinated ‘iate:s in Ohio (Befl.ar, Liclitenbeng and Kroner, 197L ) - The predc inant crgazoha.lide species was chloroform, which had a ccncentraticn range a high of 5 microgram per liter in Rook’s study(197D ) to 150 micrograms per liter in the work of Ee12.ar, et aL.,(1 74) . Is shown in table 2, trihalomethane prcd icticn originates at the water treatment plant.. !ach time additional chlorine is added to m ntaim or increase the frae chlorine concentration in water, a si ificant increase in the chloroform level results Table 3 shows the increase in concentration of organochlorine compounds in water from a sewage treatment plant following chlorination. ------- Is Table 2. Triha1ogenated— ethane Content of Water from Watar—Treat ent Plant Free Concentration, ‘ g/1 Bromo— D bro o— Sample Sample Chlorine, dichioro— chioro— Source Point p m Chloroform methane methane Raw un- treated water 1 0.0 0.9 * * Raw water treated with chlorine and a1 chlc— 6 22.1 6.3 0.7 rine. Con- tact tire 80 minutes. 3—day—old settled 3 60.8 a.ter Water flow -. from settled area to 4 2.2 127 21.9 2.4 filters ÷ Filter effluent ** 83.9 13.0 1.7 Finished water 6 1.75 94.0 20.3 2.0 from el1ar et al., 1974. * none detected. If present, the concentration is <0.1 pg/i. ÷ Carbon siur added a: : is cint. *— T,._,,__. ------- I ’ Table 3. Organochiorine Compounds in Water from Sewage Treatment Plant Compound* Concentration, ugh I f1uant Before Ireatment Effluent Before Chlorination Effluent .fter Chlorination Methylene chloride 8.2 2.9. 3.4 Chloroform 9.3 7.1 l2. l 1,1,1—trichioroethane 16.5 9.0 8.5 l,l,2—tr ich loroethylene 40.4 8.6 9.8 1,1,2,2—tetrachioroethylene 6.2 3.9 4.2 t Dichlorobenzene 10.6 5.6 6.3 £ Trichlorobenzene 66.9 56.7 56.9 from Bellar et al., 1974. * 1i. confirmed by GC—MS (gas chromatography) ------- 17 1 rhe TationaJ. 0:qanic 3accnnajssance Sur7e7 (Sy2ons et aL,1975) of 80 selected cities initiated by the u. S. Znviron ental 2rotecticn qency, eas ired the concentrticnz of six halogenated cornpounds in ra and finished water. The six compounds were chicroforn, bro odichlcro ethane, dibronochloro ethane, bro ofor , d bro c hlcro ethane, carbon tetrachlo:ide and 1,2— dichiorcetliane. The NQ S study re3ea.led the widespread cc erce of trihalo ethanes in finished drin inq water as a a rsct zesult of the cnloz nat cu process (Sy ons,1975).. Carbon tetrachioride and dichiorcethane were not for d in th chlorination reac ti on. Trihalorethane production is prinarily influenced by the nature and concentration of the organic substrate, the nature of the aqueous ChlOrine compound, pE, tenperature and Cl. IC ratio.. Trihiooethanes result frcn a reaction or series of reacticas of chlorine with preczrscr naheria? through the classical organohalide reaction or sone echanis that includes an o idatiie cleavage step. The precursor itself is not a single conpound but probably a cor p2.ex i t of hunic substances and sinple lc 9olecu.lar weiq t ccapcunds ccntaininq the acetyl nci 3t7 with differing reactiv±ti s at 7ar7 :q p 7alu s, sc lnbilities and other physical and cEe ica2 characteristics. ------- 18 The rate of trihalcmethane formation is pa dependent; an increase (toward alkalinity) in pa results in increased txihalo ethane produc-tion possibly due to an increase in the-. husic acid. reaction rate (via the classic 3echani.sin). Or possibly, co:pou.ads present in the settled water, i..e ., acetone, which are relatively inactive at pH 6..5, become significant contributors to the overall reaction rate at a higher pE (?airless et aL.,7975) . Therefore, the effect of pH becomes a critical factor Linder treatment systems where chlorination is executed at high pa, especially. vhare lime- softening or excess lime softening is practiced. Conseg ently, where chlorination follo inq clarification is carried out at pH. values near pH 7, effective coagulation and sediaentat on may be sufficient to reduce the precursor concentration to levels where ultimate trihalomethane concentrations are below the yet undefined adverse health effect levels. Where chlorination is ca ed out at high pH, i.e., lime— softening plants, treatment for precursor remove?, is more complicated. Thus, the point of chlorination in the tea .tnent process, a signifIcant fa .ctor in trIhalo ethana production, represents an important variable to be considered for change in attempts tr reduce ultir ate trihalomethane-ccnc ntraticns in finished drinking iater 2P.A.,1 4 75). Cu=ent esti at€s are that a plant can ------- 19 af ect its triha1c ethane output by plus or rninus 15 pe caut by ad ust g the point 0: cn1cr e ap 1 ca:.on. ------- 20 !xperi me ntaJ. ! vi dance of Organic Chemicai. C ar cino gen icity Chloroform’s pctentia.l for tumorigenic activity: was studied under erperimental conditions using a graded series cf necroti .ng and non-necrotizing -doses. of chioraf arm on le and female mice to determine the relation between do , presence or a.bsence of. liv r and kidney necrosis, and the occurrence of hepatomas .foUowinq repeated administration of chloroform (Zschenbrenfler and. !iile:.15L4). xidney necrosis in male sice was extensive in contrast to the absence of kidney necrosis in .fe a1e mice.. !epatomas ware observed only in female mice.. vidantly, chloroform doses sufficient to produce liver necrosis caused lethal kidney necrosis in the male rats; thus only the sur7ivinq female rats produced hepatomas.. The greater sensitivity of male mice to the toxicity of chloroform was also demonstrated by Shubik and Pitchie (195.3). iiho found under specified laboratory conditions gross tubular necrosis in males only.. In light of determining the signi ic nce of these compounds in lower doses, t e paper by ttahcni and Greenbet (1q70) was tnte:asti:g. n eiperinent vaz perfcrmed in which the filta:-sterii ed effluent cf an ------- 21 activated sludge plant was used as the sole source of drinking water for 13 rats. en natched rats whose drinking water was from the locally treated supply acted as controls. Du ing the course of the exper ent t o nale rats exposed to the effluent developed assi7e tuucrs, which was unusual for the strain of animal used. uierous alkylatinq cheaicals als.o possess tu crgenic properties. :eonq, ac ariand and Peese fl967j induced lung. adeno as i aice by chronic inhalation of Bis(chlcrcuethyl) ather . Induction of lung adena as in new—born nice by is(chi.cronatbyl)ether following asingle subcutaneous inlaction of the co poand was de oustrated by Jargus, et al (19€S) ------- 22 !pide2iolcqical !vidence for Organic Che ica.1 Carcinogenic t y 2pideaioloqical evidence subs antiating actual cancer hazards to the human population using water .ccntasinated with raccgnized snspected, and potential. : carcinogens is slight. Thorough epida io1.cgic:studies on the inpact of organic nattar in water upon hunan health do not exist. The few studies conducted relate this qua.1 ty parameter to disease by use of surrogate measures. In lo-udon, !tock (19 7) noted lower cancer crtalities i.n co aunitias supplied with well water than those receiving surface water In Eolland, Dtihl. (1S53), as part of a larger study, lookad at the ralaticu between number of cancer deaths and the water system.. ais data s gqes-ted that over the whole country there is a pronounced, though not very great difference between municipalities with or v thout water systens: those without aunicipal water zyste s possess the highest cancer death rates. Differences in cancer death rates becorne even acre pronounced if the largest nunicipa.l ties with water sys-te ..s ars e2.ininated fro the statistical analysaz.. The average cancer rate for all 3un1ci alities ------- 23 w±th water systems decreases fto 585 to 543. Duh.l (1953) divided the main sources of water supply in the 1etherlandz into four çroups river water, heath water, dune— zatsr, and we.U. water. The average cancer death rate varied frog 606 (river water) to 594 (heath water) to 585 (dune water) to 568 (well water) per 100,000 population. In !ugland, Davies and Wynne—Grtffith. (1954) invest qated the distribution of salignant neoplasns of various body sites with relation to the kinds :cf soils at the hoses of persons who died of cancer i the County of Anqlesey during the 10 years 1 3—1952 Th firzt st idy (195Z -.) found that cancer of the stouach nd breast .a3sociated with gro 2p soil series, water supply and social class. The secend study (1954 ) fcund that the association with soil, in the case of sto acb and breast cancer, was independent of social group and water supply. - Of particular interest s- whether any of the haloqenated coapounds found in drin iag water are also present in hunans ingestin; such water over long periods of tine In a recent investiqation Dowty, Carlisle, Lazeter, and Store; (1975) studied halogenated h7d;ocarbcus in ew Orleans drind nq water and in blood plasnas cf area residents. Thirteen haloqenatad hydrocarbons - er identified in the driking water; fiie were identified in tne piasna. tchl :oethylane and carbon tetrachlcti a were found in both piasoa and ------- 2 drin kinq water.. Considerable daily variation - —in the- concentration of halcqenated hydrocarbons in the d.rinking -water was noted. The a1or halogenated hydrocarbons isolated fron ew Orleans drinkinq vatec -vera: 1- :chloroproper.e, chiorofora, carbon tetrachioride, d.j ch .loretha ne, tric hioro ethylene, dichioro propane, dichloropropene 1 brodichloro ethane, dichioropropene, tetrachicroethylene, d bro cchlorcaethane, . :1 a ctichlcrcpropene. Prelirninary studies showed carbon tstrach.lcride- and tetrachiozoethylene present in :the pooled plasma of two test 4ronps with concentration of carbon tatrachicride substances higher in the-plasma than in drinking water.. In view of the lipophilic nature of cblorofor , Dovty sugqests that a bioaccuau.].aticn aechanisi ay be in operation, if drinking iater is the only source of such 3aterials. I study by paqe and EaQrjs (197Z ) involved an investigation of county (parish) mortality rates for Louisiana, 1950-69, f or tota.l cancer and selected cancer sites in white males.. Counties were categorized as to fraction of the county population drinking from the mississippi iiver . . I regression analysis (unwe ghted) was used to terni e t a cancer risk attributable to use of the rnississippi ‘iver water cr drinkinq. ajor cancer sites included in the stud7 were: total cancers ninas lung cancer, urmnar7 tract, gastrointestinal tract, ll7er, ------- 25 and lung. The analytical procedore controlled for rural— urban characteristics, median income, population density, and proportion of employed population in pet:oleu industry, chealcal industry and aining industry. eqressicn results for total cancer shoved three s qnificant va .ables with the “expacted signs: water(+), ercent rural(—) and inco e(-). The addition of the occupaticual iariables to the total cancer regression had little inpact.. In the regression eguation for urinary organs i he water and urbanizaticn variable as significant, while income was not.. With the inclusion of the occupational variables, only the che2ical industry 7arible as zig nif ica nt. Begressions of gastrointestinal cancer mortality (sto ach, large intestine, and rectum) exhibit vater(±), urbanization (—) and inco e —) 7ariables as significaat Aqain the chenicaJ. industry variable was significant !egrassicns of liver cancer showed no relationship with any of the wariables. Peqressions of lung cancer ortal1t7 showed ‘iatar(+) and the urbanizaticn(—) variable as significant Cccupaticnal variables, when added to the equat on, were not gn .ficant second st d7 (Pace and Eanris,1973 was perfc:ned with inde end :t ia.niables sinilan to the fist fo: total cancer, cancer of .nnrv organs, and cancar of t ------- 26 qastrci testjnaJ. tract for both sex-rac groups.: total 2c tality rates, the drinking water variable was significant for aU groups except white fenales; the urbanization variable was siqn.Uicant for aU :fow :qrcups; the. income variable was significant only for white ales..- cancer of the gastrointestinal tract, the drint i ng water variable .was statistically significant :in all f ur pop lat±on groups. Ccnsidered separately, dr in g-. 2vat significant for cancer of the rectum and stoaacb,- : t ot the large intestine, in nonwhite na.].es and feaal:es; large intestine and rectum, but not stoaach,; i whtta fa ales; and rectun, but not large intestine and stoaach,: in white mai. .es. For cancer of the rinary -Or a .nSr drinking water was a significant variable on in white sales and nonwhite fe ales . For total, cancer mortality rates , the three occupational variables (petro.leua, chenical, :ining do not add to the variance explained ncr are they significant. Page and Earns (1975) snggest that the lack of significance nay exist because only a fraction of tha..work force is in any of• the three industries and thas the occupational effects are buried in the aggregate data.. owerer, for both cancer of the ux±aazy organs and qasto 4 ntastinal tract the chen.ical industry var .able is significant (table !1). The investiqators cnnc.l ded that ca nogens in drinking water ara in suffic±e t] y high cuncentrati3ns t ------- 27 e danqer human health.. Taro e and Gart (1975) reviewed “ he I plicaticas of Cancer-Causing Substances in !ississippi iiver- ‘ater..” Tarone and Gart’s stud7 included n additicnal variáble: :aleyatjofl above sea level, refined the reqress ion ei:b usiing weighted regression and expanded the. an.alysLs::tø r ce—se groups not inittally studied by aar is-(tabla 5) ------- 2, Table 4. Regression Coefficients 4 for Variable Representing Proportion of Drinking Water from Mississippi Cancer Sites WM NMf WY NWP Al]. sites 32.5* 49,5* 3.0 29.3* Lung 7.5 All other th ].ung 25.4* Urinary tract 3.6* 1.6 1.5 2.7* Gstrointes e(n l 7.0* 19.4* 4,9* ‘73 3* Liver 0.1.5 from Page and irr s: * Coefficient significantly different fran 0 at 3% level. Di ensions of deaths per 100,000 per year percent of ‘ atar :f ran the Mississippi. Table 5 , Results: Presence (*) or i bsenca (NS) of Statistical Signifi— cance at 5% Level for the Variable Representing Proportion of Drinking Water fran Mississippi River. Significance of Regression Coefficients 1WM WY NWF * NS * Cancer Sites M All sites * Lung * * . TS * Ganitour i nary N5 NS ‘IS NS Liver NS S NS NS fran Throne and Gart, 1973. ------- 29 Tarone and Gart do not recognize a : causal relationship between water source and cancer 2ortaIity for the follcwinq reasons: 1) the hypothesis that the liver, havinq been de2onstated as a prime target:; organ in experimental ani l s-tudies for organic chemically- is duced :hepatomas, would be principally affected in populations: beinq served wi surface water has - not been substantiated., 2) the time sequence of cause !ississipp i liver water) preceding the hypothesized effect: (canter) has not been established (data is not available: accurately datersine when, in time, the suspect carcinogens were present in water nor the quantities and nature of the specific chemicals themselves) ;3) :tha study was ecological: the variables used are -; descriptive properties of qroups and not descriptive properties of individuals, i.e., proportion rural, median incona and population density. The anato y of the ecological correlation is such that tbere need be no correspondence between the individual correlation and the ecological correlation; 1 ) the relationshIps between the various cancer sites and water variable lac c consistenc7 across the. four sex-race goups here is no adequate explanation for the significant results obtained far gastrointestinal tract nor why, far total cancers, white females do not show a significant asscciation with the iiater var .a2le. If the latter results are valid and if ------- 30 drinking water is to be considered a causal. factor- cancer mortality, then an explanation for deceazed water consumpticn or less susceptibility to potential water carcinogens by white feaales aast be given. • DeRcuen and Diea (1975) did another analysis - of cancer in Louisiana with the. izsissippi Pi er: Las drinking water source. 3ecause of known sicecono ic- ethnic differences in Louisiana, the in4estiqators included an additional. variable • latitude, thus dividing Louisiana into northern and southern counties.. . rban- rural characteristics, sedian inc e, : : eaplo ynent characteristics and elevation above sea level,: v iabIeS found to be statistically associated with cancer ortalit’ !n the studies of Page and Harris (1974.1975) and Tar ona and Gart (1975) were not included in the a.nalysis by De3ouen and Dies.. The water variable was treated as a sisple dichotony, i.e., none of the water obtained from the mississippi Piver versus all or some fros the Hiver. This handling of the water variable was in contrast to the previous studies focusing on proportion of population using the !iszissippi !iver as drinking water source.. DePonen and Dies concluded that those counties in a. ‘— Louisiana being r’ ed drinking water from the !ississippi Biver do have slightly higher cancer rates than those receiving water fran other sources.. Eowever, there nay he a aultiple of other causes than that c water guality ------- 31 contributing to the differential. Bu rher (1976) in a study of Cincinnati drinking water constructed a regrass ou analysis of the cøunties of ohio in the an.ner that the regre.ssion for t.Ouisiana v constructed by the niro nmental efense rates were regressed on variables: propOZtiOn tnra2 -ae4ian inco e in S1000’s, density of population- p na e- gil., and occupation. Occupation variables p .ayed no role in the regression equations. The residuals were inspected to dater ine fT:: patterns were present. The residuals were iew d- asthe cancer rates after adjustnent had beefl : de fcr differences in proportion rural, edian.:ift and. population density . The urban/rural variable enta ed the regression results most frequently: 1.11 Cancer-W , W Y: .Lu’nq—-W!; Sto ach-- ; 3ladder—- ! and W?; Iidney-—W ; Large Intastine-—W . Density of population per square aile entered the regression results for All - Cancer-—WZ ; -Pancraas——W ; Lung —Wy; Large Intestine — —Wi!. . For the variable aedian income in $1000’s the following sites were of interest: Pa.ncreas—WF; !ladder—-W ; Sto ach— —’WL When the cit7 of Cincinnati was co parad to Colu *is — 4. and Cleveland and anilton Courty was cc pared. to Yrank.lin and Cuyahcqa Counties, the death rates sai.iqnazt d seasa did not seefl to have any :elaticnsh!p to any of the findings concerning drinking iater. ------- 32 In conclusion, drintinq water from the Ohio iver:was not: associated with cancer death rates higher than cenc r death rates frcn other sources of drinidn g water f3uncher.1976). Other investigations studied the relationship :between chloroform concentrations in d.rinking water :afl :canc acrtality rates. cCabe in 1975 chose 50 of :t a S0 cities .participatinq in the ICES study for further i vt1qatioxr. Eaquirements for each of the chosen cities were a : :t9 50 population of over 25,000 and 70 perceat ormore of the city’s population receiving water comparahi. e .t that sampled by the E.P.A. !cCabe found. a. .ztatistica11y siqnifica ’tt correlation between the -chlorofo: concentration In drinking water and the :aqsez—race- adjusted cancer mortality by city for all cancers combined. - Similar results were obtaine d by 3uncher (7975) for aLl cancers in white males and. chloro orn concentratior.z in 23 cities having populations of 25,000 or more in 1970. Lisa pancreatic cancer death rates in white males and chieroforn concentration had s-tatisticaLLy signifIcant correlations for 77 cities- specificaLly for 59 cities vith surface water supplies and for cities that contained more than O% of the o ty s popuiation Per cities with greater than 70% of the county’s ;opulaticn. there was a significant correlation between choroforn concentration ------- cai TH3 ! UI1LZ A 1D !ZTEODS ------- 33 and bladder ca:cer for white males and white females., To sunmariza: studies by the 3nvironmental Protection gency have affirmed the large number of arq nic chemicals present in public water supplies . Whjle- th ,; potential health hazards of many of these che icals are .-; unknown, others have demonstrated carcinoqenic activity in laboratory animals under experimental con4iticns; still others have, in limited ses,: been implicated in causinq cancer in hunans.. The lar e scale a pidemioloqical studies, to data, iave—-at best- -pcintad to an association betweea sourca of. drinkinq water and cancer nortality. Rowaver, the. data has,. in general, lacked consistency and coherence., rose-- response curves have not been ascertained nor has the question of temporality been adequately addressed.. ------- 35 1TZ2I1LS The qeoqraphical area of the present - study incorporated 3 6 counties selected fom -seven states (Illinois, Indiana, Kentucky, Ohio, syl’rania, Tennessee and est Virginia) having a total pcpulation in 1960 of 18,721,791. Selection criteria for counties was location vtthin the boundaries of the Ohio 2iver Valley Dazin as deta:ni .ned from state maps and vater drainage maps. ?cur counties in Virginia, initially selected for study, were deleted since two of the four counties had aeen merged in census data.. Y tal Statistics crtality ata nsed was the race, sex-specific direct aqe—adjisted. death rates for the 3056 counties of the ccnt qucus fl. .S.1.. over a 20 year period, 1950—1969, available from the National Center for ealth Statistics, 3ock villa, Maryland in D e publication no.. 31! 7ti 615 . Corresponding county populations were provided by the 1950, 1960, and 1970 censuses with interrensal estimates derived by linear inter;olation. !or thi ty—f ve can r tes, age—standardi:ed crtality rates by race and sai in each county had been caic .latsd; the standard. beinq the age t. uticn of the 1960 ------- 36 pQpuj.aticn of the 7.5. Cancer sites were classified according to the Sixth evisjon of the nternatjonal Classification of Disease. he cancer ortai.1ty data was available on tape from the ationa1. Cancer -Institute . J acb tape record has six variables; the nunber -of reccrds. for any one:county may vary from 1 to a aaxi aum of 140: (the number of possible ccmb nations of sax, race, and: cancer sites is 1Z 0). Cancer sites (Internat cuai. Classtfication : cf Disease,6th ed.). Chosen for study were: esophaqu.s (150), larqe intestine, except rectun (151), rectun (15L ), biliary passages and liver (155), pancreas (157), laryn: (167), trachea, bronchus and lung specified az prisary; and lung and bronchus unspecified as to whether prinary or: secondary (162,163), breast (170), prostate (177), kidney (180). bladder and other urinary organs (181), Eodgkins Disease (201), lynphosarccma and- reticulosarcoma (202), multiple myeloma (203), leukemia and aleukemia (204) and all. malignant neoplasns (140—205). A file of the cancer sites was created from the original, tape with 68 of the possible 1 0 combinations (due to the elininaticu of sorne cancer sites). iflle of al ]. couties in the seven study states vith selected. socic-deuograpI .ic data was eated.. he zccio-de r pbic data was obtained fron the City- County census books ( S) available on .tape . aria.blez selected included: ercant urban pcp J.at±on, :uu er ------- 37 eapl.oyed in aqiculture, percent employed in inera1 industry, numbex enployed in the anufact’ure of non- durable goods, total population, population per squa.re mile, percent non-white, median age, median number of yee.rs of schoolinq completed by the population. iover the-. of 25. median income, population change (tótaLand percent), percent foreiqn stock.. Public water source data was obtained f oz- the T.S.P.E.5. Public ‘water Supply Survey Publication, no. 775 1963 which provided water in rmation oü’ communities (listed alphabetically for each state) tbroughout the 11.5. I formae.on includes population (1.960), source -cf the: public water supply, number of people servedand vatar treatment data. !ach community in the study state of the Public iatar Supply Survey was identified with the appropriate county by referring to the 1960 census p bl.ications .A county card. was developed with the f i1cwiaq information: state, county, 1960 county population, source of water supply, estimated coamunity population served by this source and type of wa -tsr traat ent with the estinated ccmmun t7 population served by such vat r treatment. Community pcpulatian figures were validated against 1960 census data; the estimated. population served by a specific water source was made using individual state water data obtained from t e !nvj:cnnental protection ) gency, Cincinnati. ------- 38 check was 2ade of all connuaities not ‘atched in both water publication and census sources--the 3ajority of these coa unit±es had populations of less than 1000. Of the; 3 6 counties initially selected, eight had no water data. Of these eight counties, six had no nnun ities yLt1 populations greater than 1000. Of the re .aining two, one county had a single - coasunity of a size exceeding 3000 people and the second county had one coa.aunity with a population of slightly over 5000 people. ecaase of the larger ccunnity population it is assused that the water data is aissinq rather than being totally dependent on private wells. Thus, of the counties with some proportion of hair population unaccounted for with respect .t - water supply data, nforaation frorn census zoo.rces on, pcpulatLcn size and private coanunication ( cCabe,i 976) would indicate that most are served by private wells. Initially, for each county, public vate supply sources ‘were cataqo .zed ±uto six groups: a or rivers (defined as ajc: t .butaries of the O ia 9iver) • ±nor rivers, wells, lakes, springs, and unknown. The total and percent population being served under each of the categories was calculated. iqa.in, for each county, public water supply sources were categorized by the co2annity’s type of water reat en L ?our qrcups were eated: o chlorination, p:ech lc ation, poztchlcri ation and both ec1lorinatioi and poztchlorinat .cn . The total number of ------- 39 :people and percent of population served by each treatment ” process was computed. and recorded.. The operational water variables were 1) percent s f ace water usage (nunber of :peop].e receiving tbeLr public water supply fro3 a1or and :iin Or rivers divided by county population tines 100) 2)’. percent prechiorination (unaber of people drinking water that has undergone precklarlnation and - 1 /cr both prechlorinatjou and postohioninatien bined divided’ ‘by county population tines 100). In assu ption regarding the- f crier is that the percent of the county population whose-. source of water was unknown was, in fact, servedby:water: froa sources other than rnajor and amen rivers..- The three original data sets coapnised:— (7) water data file on cards for 3 6 counties (2) aggregate cancer file on tape (3) census file of socio—deaographic varia les The water records were ‘sorted in ascending order according to population si ze. 12 state codes oi atar records and census records were inconsistent, all record IDs of the cansu file were printed and the corresponding state ccde frea the water files iere then aerged to prad e a coaposite wcrk ng f±1e ------- T The study focused on two different predictor tariables (percent surface water usaqe and percent prechlorination) using thee as test variahies in successive order. To analyze the r2lattonship ‘between age—adjusted cancer rates (site, race, sez-spe .fic and.- the. water - vairabla cf interest, unweiqhted ul tple regression analysis was performed . The county was the - unit of study. The denoqraphi’ variables selected for inclusion were: percent ncn-white population, edian inco te, median number of years of schooling completed by the population over the age of 25, number employed in aqriculttxre, number employed in non—durable manufacturing, population per square sue, percent urban pop L1ation, percent foreign stock and percent employed, in aanufacturi ug. 3ecause of the extreme variability of the size of the individual county populations, weighted regression a— . analyses were used on the same data mats as in the nveiqhted regression procedures.. For each coun-ty, the weighting factor was the square rOot of the tot county pooulation which, under specific aszu pti ns, will be ------- 41 inversely proportional to the standard error of the 2crta.Lity rate (Rcover, 1975). While it is preferred to use the square root of the appropriate sex-race strata of the total 1960 population, the data file being ezployed did not contain a sex—race breakdown for- the cOunty population and total population figures were substituted. However, this substitution would not be a ajor problem given a sax-ace ratio constant across the study: count es 1 .: The-usa of the total population in this study :2ay be reasonable qiven a recent report ( ogan et al . ,1 76) where regression analyses co ;aring weights using total county population and sex-race county popui.ation figures for - Region V counties showed no conclusions were : altered by the choice of total population over sex-race spad.fic totals. Pollcwinq the prelininary screening procaduzes by unweighted and weighted ultip1e regression procedures, the reqress cn cdel was re ducad Those cance.r sites having a. p—value of .10 or less (pcsittve direction) based on the standard t-test were selected. or the individual cancer sites selected, socio—econosic variables having a two sided p—value of .20 or less based o the standard t- —t. test were chosen. llso, ste wise regression results were considered Re;eated analyses were done relating cancer orta1ity of s;ecific cancer sites to percent surface ‘later and t e ------- yarious explanatory variables in the reduced aodeL. mother set of analyses iere perfor2ed for the sane cancer sites and. de2ograpb.ic ;a. .ables but substituting percent pechiorinaton for percent surface water usage. Treating percent surface water usage and perc ent prechlorination successively, sone groupings of cancer sites were carried. ont. Por each race—sex g p, w.eiqhted reqressicn van dcne on the coabined cancer act lity at2s- for la:qe intestine and. rectus, for the urinary tra (kidney and, bladder and other urinary organs) and qastrointesti.nal tract (esophagus, stoaach, large intestine ar4 ractn ) use, because of possible bias in the cancer aortality data of large intestine and rectum due.: to differences in diagnostic reporting, slaba ling and raq onal differences, large intestine and rectua were combined. Pollowinq these procedures, as a ude surrogate aeasure of the possible.. inpact of air pcllut on and sacking, lung cancer ao taIity rates were included in a series of regressions as an independent 7ariable.. Given an expected iapact of population size on cancer iortality rates, the study counties were grouped into three -trata based on population size: less than 50,000, 50,000—250,000 and over 250,000. weighted regression analyses using the reduced node.]. was again eucc szi7ely sad fez percent surface water usage and percent prec hiorina ti on ------- Thee to increase precision, these ana3.yses were repeated select±nq only those counties for inclusion in which 50 percent or nore of the county’s water sou rce w s known.. ------- ------- 45 P C2 T S ?1CZ WIT2B ZiG The results of the esticated percent surfaca water coefficients from unweighted and weighted re.qressjcn aalysez of the four race—sex groups are su arized as follows tables 7,8); 1.. except for lymphosarcoma S reticu.lcsacco a ‘in white males and. multiple myelcma in white females, whetber the presumed percent surface water usage is significant or even su gesti7e for any given site depended cn whether unweighted or weighted regression anal yses vere ernployed; 2. with un eiqhtad regression procedures, percent suface water usage showed weakly siqnificant or significant positive statistical association with the follcwinq cance r sites (t bl s 7,$3): in ifl .ite males, lymphosarccma & reticulosarcona {p.096); in white females, multiple myeloma (p.077); in non—white males, rectu3 (p=.077) and pancreas (p=.025). In non-white females, no significant asscciat on was found. 3.. with weighted :eqrsssicn procedures, percent Surface •iater isage shovad veakly significant er sigmi.ficant positive statistical asscciat cn itb the following (tables 7,8): in white males, esophaq ------- (p=.O 1) , large intestine (p=.053), recturn (p=.015), larynx (p=.003), trachea, bronchus & lung (p..O15) * bladder S other urinary organs (p=.013) , lymphosarcoma & reticulosarcoma (p .Q72) and all malignant neoplasas (p 4 .OOO); in vhite females, rectum (p...OO7}, breast (p. ..1OO) and multiple ayeloaa (p=.068); in. non—white aa.les, no significant positive associations ‘were -obser ad;- in : non—white females, esophagus (p .=.350) and: : l ary x (p.088) 4. except for rectal cancer, prelininay regression procedures aanifested no consistency across r ce-sez groups ncr was there a pattern by sex or race (ta.ble :6). 5 . the sixty—six regressions (unweighted and ‘we qhted) evidenced a greater number of cancer sitas as significant than would be expected by chance alone only for white males (weighted regressicu). The weight, w , asscciated with the ith observation, , is a measure of the. relative importance of the observation in the final rasult Usually the weight is taken as the reciprocal of the variance so the observations with the smallest scatter are given the greatest weight. lssuxinq the àbservaticns are unccrrelatsd, this procedure gives the best estinate of the pcpu..lation rnean, i .e., an unbiased esti.uate with jz±mu: variance (naxi un precision). ------- I7 In this stndy, because of the great variability- the size of the population at ris , each county observation vas veighted by the square root of the county popnlaticn:— - every variable in the observation—; was 2ultiplied by the weiqht. ------- 4, Table 6: Siir ry of Significant Results between Percent Surface Water Usage and Site, Race, Sex—specific Cancer Mortality Rates, 1950—1969, in 346 Study Counties. -: W 1ITE NON-SMITE Cancer Site Male Female Male Female Esophagus S+ MS MS S+ Stomach MS NS MS MS Large Intestine MS MS MS Rectum S+ S+ S’ -MS Biliary P 2 ssages MS NS MS -- MS & Liver Pancreas MS MS S’ MS Larynx 5+ MS MS 5+ Trachea, Bronchus S+ MS MS MS & Lung Breast NS MS NS Prostate MS MS MS 1 MS Kidney MS MS MS MS Bladder & Other S+ MS NS MS Urinary Organs Rodgkins Disease MS NS. MS MS Ly phosarcoma & S + MS MS MS Reticulosarcoma Multiple Nyeloma MS S +• MS MS Leukemia & MS MS MS MS Aleuk ’i AU. Malignant S+ . MS MS MS Neoplas s p—value based on standard t—test * significant p = <.10 C or e-tai1ed test), unweighted regression + significant p = <.10 ( on tai1ad test), weighted regression ------- +1 ¶able 7: £ tienc.d Perc. nt Surface Water Usage Regression Coefficients and Associated p—values froa Ut— weighted sad Weighted Rsgr.esion Analyses of Whit. Males, White ?enzles and Site—specific Cancer Mortality Rates Versus Selected enographic Risk ractors for Malignant eoplasa Mortality, 1930— 1969, in 346 Study Countiu. ITE MALE WRIT! FD ALZS TInv.Lghced Weight.d R.gr.s sio Regression P • 0407 • 0006 - .6923 .0003 .6350 .3830 —.0037 .308T —.0043 .1532 .0526 .0001 .9272 —.0020 .7329 .0153 .0011 .7984 .0067 .0068 .4892 —.0045 .478]. —. 0003 .8100 .5143 .0007 .3675 .0032 .2213 .0033 —.0001 .9392 .0008 .1100 .0134 —.0023 .6190 .0025 .3269 .3027 —.0034 .7260 .0095 .0993 .3621 — — — — T nw.ighted Weighted Uaveighted Weighted Regression Regression Regression Regression 3 p* 3 p 3 p 3 Ridney .0024 .5063 —.0008 .6845 .0030 .3052 .0006 .6598 Bladder 4 Other Urinary Organs .0054 .1774 .0062 .0133 — .0007 .7333 .0018 .2206 Sad girins 3iseua .0009 .7473 .0022 .1683 — .0019 .3468 .0017 .1077 Lyaphosarcoaa & R.Uculosarcoss .0062 .0962 .0038 .0720 .0015 .6279 .0004 .8301 Multiple Xytlans .0000 .9901 .0016 .2171 .0036 .0773 .0020 .0679 Leukeeia & Aleukesia —.0013 .8333 .0017 .5856 —.0033 .4972 .0018 .4493 All Msi.igaanr M.ap1a .0200 .3556 .0784 .0004 —.0218 .4504 .0203 .2533 rtvo aided p—value based on sta945x4 t—test. Duv.ight.d Regression P. Weighe.d Regression I p !sophegu. Sto.ech erg. Intestine Recth Biliary Passages & Liver Pancreas larynx Trachea, 3r nchus & lung Breast ?tost*te .0015 .6432 .0039 .0039 .6381 .0007 —.0061 —.7219 .0106 .0027 .6263 .0079 .0004 .9425 .0019 —.0015 .3022 .0023 .0021 .4063 .0042 —.0069 .6377 .0234 .0006 .8925 .0003 .0035 .7188 .0010 WRIT! MAL23 p I ------- 50 Table I Esifzatsd Percent Surface Water Usage Regression C3efficicnts and Associated p—values from aveighced and weighted Regression Analysis of on—vhi:e a1es and on-vftit. Fenalas and Sits— Specific Cancer Mortality Rates Versus S*lected D ographic Risk Factors for Ma i; snt ‘ ecp1aas Mortality, 1950—1969, i 346 Study Counties. M0 -W8ITZ MALTS 7ZM—WaITE 7 tALES misigttt.d Weighted Unveightad WeiZhted Regression Regression B.;rasaion Regress1o a a Epitava —.0007 .7833 .0071 .6758 ..0016 .8187 .0107 .0499 —.0019 .3468 —.0297 .3063 —.0219 .3028 .0122 .5481 Large Intestina .0015 .6279 .0063 .9121 0644- 3855 - 0471 .4854 .0036 .0773 .0336 .1527 —.0227 .3912 —.3114 .4324 3i2.iary Passages 4 Liver —.0033 .4792 .0031 .8754 —.0230 .2659 —.0249 .0672 Pancreas .1145 .3246 .0477 .1629 —.0201. .5572 —.0092 .61.86 Larynx —.0123 .3633 .0063 .6203 .0087 .1123 .3071. .0385 Trachas, 3roachus S Lung —.1444 .2873 —.1070 .1327 —.0924 .2312 —.3305 .2979 3reasc .0004 .3624 .0019 .1697 .3544 .3823 .0239 .6742 Prostate .0129 .8764 — .0073 .8903 — — — $— RZTE MALTS ? N-WHIT! F ALZS Ucw.ight.d Weighted Unveighted Weighted Regression Regression Regression Recess i on 3 p 5 3 p 3 p 3 p Ridney —.0256 .6063 —.0330 .1799 .0134 .2284 .0027 .6679 3Ladder & Other Urinary Orans .0360 .4177 .3078 - .6697 —.0182 .3698 —.0288 .0503 ffodkisa Otsess. .0054 .5867 .0007 .9060 .0083 .2626 .0016 .7170 Lymphosartoes 4 leticuloearcama.0337 .1137 .0236 .0387 .0009 .9794 .0029 .3791 Moltipi. Myelcna .0068 .7796 .0068 .3244 —.0010 .9384 . .0069 .4139 tsuk. a 4 A1auk a —.0369 .4863 —.0011 .9680 .0128 .7855 .0117 .7333 All. Malignant ¶scplaans —.1102 .7216 - .0348 .8316 —. 0684 .8112 -. 322.4 .3840 ‘Tvo— i4ed p—valu based on sraj datd :—vsst. ------- 51 PoU.owinq preli inary n’veighted and. weighted a aj.yses, several. individ a.]. cancer sites ware combined since relatively by site—specific cancer mortality could result in bo numbers.., Also, combining several individua.l cancer sites-allowed, us to analysis related organs, i.e., - o qan systems.. Since experimental and epidealoloqica.t. studies (!hthik S Pichie, 1953; Page arris, 1975k - indict the gastrointestinal and urinary tract syst9 s as - potential prime ‘targets for ca.rcinogenic activity, for each sax—race group, weighted and we qhtad regression analyses were pezfoz ed on several sites combined into two systems; esophagus, stomach, large intestina and rectnm comprised the qastrcintestinal tract system while id.nay and:-- bladder & other urinary orq ns comprised the -mrina ’y’ tract system.. In whites, the gastrointestinal tract shoved a s±qnifLcant statistical association (p.,013), table 9) for males ‘when ‘we±ghting was used——a result consistent with data f:c the ind.i7idua2. sites... urinary tract showed no positive association in ‘vh te males,. Neither system shoved a positive siqni f cant association for other race— sax groups (table 9,10). ------- 51 Table 9: Est -m- tad Percent Surface Water Usage Regression Coefficients and Associated P—values fron Unweighted and Weighted Analyses of the Gastrointestinal and Urinary Tract Systems Cancer Mortality Rates Versus Selected Demographic Risk Pactors for Malignant Neoplasn Mcrtality, 1950—1969, in 346 Counties. w TE MALES WHITE PE !ALES unweighted weighted unweighted weighted regress ion. regress ion regression regres sion CancerSites p a p a (Reophagus, Sta ach ç .0013 .9224 .0230 .0.29- —.0059 .6431 .0007 .9211 Large Intestine Ract Bladder & —.0010 .8981 .0043 .3414 —.0038 .6120 .0024 .5615 Xidney *t ...sided p—value based on standard t— test ------- 53 Ta 1a 10: Estina.ted Percent Surface Water Usage Regression - Coefficients and Associated P—values from Unwaighted andy Weighted Analyses of the Gastrointestinal and Urinay Tract System Cancer Mortality Rates Versus Selected Demagra hic Risk Factors for Malignant Neoplasm Mortality 1950—1969, in 346 Counties.. NON—WRITE 4 L c N ITE FEMALES unveighted - weighted imweighted weighted regress .on regression regression regression - CancerSites p p (Esophagus, / Stomach —.0548 .7093 .0173 .8242 .0185 .8824 .0585 .4173 Large Intestine Recti . Bladder & .1047 .1004 .0508 .2922 —.0429 .2887 —.0341 .1589 idney *two_sidad p—value based on standard t-tast ------- 5* Having completed the preLisinary analyses (tables 7.8). specific cancer sites and associated indepandent variables were - selected for f -ther analysism I reduced cdel unique to each site was tasted since.independeat varIables were not consistently significant :a os3 all specific cancer sites. The “reduced cdal” includad, for each race—sat group, only those cancer sites associated: vith percent surface usage at a level of p<. 10 tone :sided): based on the standard t-tast.. The criterion for inclusion of de graphic variables into the equation was a two—sided p—value of p<.20. Stepwise regression procedures :were. also perforaed as a means to sale ct the appropriate yaniables. Thus, for each selected cancer:.site, - the selected denoq:aphic variables would be specific to that cancer site. Overall weighted regression analyses on the reduced model had sin .rnal impact or. the regression coefficients and associated p—values. The size of the regress icu cceffic ents and associated p-values for the esophagus, large intestine, rectum, larynx; 1 q, bladder and all aliqnant neoplasas In the whIte 3ale underwent lIttle change. The only site significantly affected was lynphcsarccra & :e .culosarco a which changed fron wea cl7 siqnif cant in the full regression :odel to n-cr.— significance In the reduced cdel: p=.O72— p.l 8 2 (tables 7, 1 1) ------- 55 3zcept for breast cancer, little difference observed in the respective sites in white females between the full and reduced modeL. In the reduced model, breast cancer mortality had a statistically siqnif cant association with percent surface water usage of p+.000 while in the full regression model, the association was only weakly significant. The respective regressicr coefficients more than doubled (tables 7,11). xanining the variables that had been present in the fuil model. but removed from the reduced model, four of the five ($employed in non—durable manufacturing, population per square mile, % urban population and % foreign stock) were significantly correlated, p=+ .00 0 , with both east cancer and percent surface water usage. hns, it is possible that percent surface water usage is acting as a partial surrogate for the deleted variables. In, non—white males, the panceas which had been significant in the unweiqh ted (but not in the weiqhted reqrassicn) in .the full model was now significant (p.032) in the weighted re.gression with the reduced set of variables- In the reduced model, rectal cancer mortality re*a red unchanged from that of the full model (tables 8,11) No apprec ble change in regression c efficiantz and associated p—values were seen betzeen the full and reduced weighted regression rodel in noa—white enales (tables 9,11). ------- 56 hi1e u1ticcUinearit7 was a p ob1e i a eng the indepa dent va iab2.es, the overall lack o cha qe in the reqrassicn cce fficientz when the 2odei was rednced indicated that the variables Gxcllidsd fto the f iU. od.el had little effect on the water csage factor. ------- 57 Table U : Est atad Percent Surface Water Usage Regression Coe ffi— dents and Associated p—values* fron Weighted Analyses (reduced model)+ of Selected Sex—race, Zita—spec fic Cancer Mort T{ty Rates Versus Selected Demographic Risk Factors for 1 a t Neoplasm Mortality, 1950—1969, ±n 346 Counties. Non-white White Males White P ’m 1 es Non—white Males F 1es Cancer Site p p p Esophagus .0038 .0412 .0103 .0267 Large .0092 .0808 Intestine Rectun .0071 .0269 .0084 .0006 .0213 .2270 Pancreas .0464 .0380 Larynx .0047 .0006 .0047 .0818 Trachea, .0238 .0034 Bronchus &Lung Breast .0250 .0001 Bladder & .0053 .0148 Other Un— naiy Organs Ly phosar— .0020 .1313 cona & Reti— cu losarcoma Multiple .0019 .0562 Mycloma AU Malig— .0810 .0002 nant Necplasns * jc sided — alua based at standard t-tesr + inclusive criteria: p <.10 in full cde1, posi:.ve direction ------- 58 Differences in diagnostic raport ng, islabeling and regional differences nay have caused bias in the cancer 2ortality data of large intestine and rectun. And, since rectal cancer mortality was siqnificantly associated with percent surface water usage for three of the four race-sex groups and since large intestine was also positively associated with percent surface water usage in white males it saeiied necessary to run another set of analyses with. large intestine and rectal cancer mortality combined.. Rasu.lts frog coabining the two sites were relatively. consistent with outcc es from separate site analysis., o statistically significant results were obser7ed with unweightad rea:ession procedures for any race-se: group. With weig.hted regressIon procedures, large intestine and rectun together produce a positive statistically significant association (p-=.O11) with percent surface water in white gales. ll other race—sex groups shoved no significant association (tabte 12) - ------- 6q ab1s 12: w.thtM and vsi bc.d R* ession a.1yi.s of ?* ent Surfaca ats Usa. s and C02— bin.d sires: t. ,. Intu Un. and ac f r a.U. ac .—s .x gra aacz/sE C. TC! SI! J.i,titsd 3 P nit. a.te — .. 32 .7541 . t:3 t.hL:. T .L. —.0007 .9451 .0047 .4ô 8 ou hi . a1 . —.0349 .7761 .0399 . 645 !on Whits Yenala .0419 .7290 .0356 .6074 * Tvo—sLdsd p—va1 as based on standa rd t-t.sc ------- 60 ‘ost cancers have a aultiple etiology. hr pollution and s:oki.nq are potential portant confoinders in the present stndy. !ince an adequate index of air poi.lut cn on a ccu ty level vas not. available and since data on stoking were alac lacking, a surrogate ceasure for both air pollution and saoking was used. This surrogate aeasure, aqe—ad usted lung cancer mortality rate, was included in the reduced weighted reqressicn model as an independent variable and regression analyses were repeated. V With arcent surface water as the var abla of interest, it is important to iicte that the overall pattern of relationships remained stable (tables 11,13). ?cr white V males and white females, the direction, size and associated p—values of the regression coefficients re3ained relatively constant.. For non—vh tes, female esophagus and larynx and male rectum did. not shcv a malor change. Only in non-vh.ite aJ.e pancreas was there a siqn reversal (3:.O 6,- _ ’:.O59) in the estimated regression coefficient.. ------- ‘Pt Table 13 : Lsti ated Percent Surface Water Coefficients and p—values for Cancer Site by Race—sex for Weighted Regression At yses (reduced model) Including Lung Cancer Mortality as a Predictor Variable. Race—sex Site p_ralue* White Male Esophagus .0033 .0632 Large Intestine .0119 .0276 .0063 .C447 Larycz .0044 .0011 Bladder & Other .0065 .0042 Urinpry Organs Ly pbosarco a & .0005 .7820 - Reticu1osarcc a All Ma1i tt nt .0389 .0236 Iceoplas s White 1 e .0072 .0032 Breast .0187 .0001 Multiple Mye1o a .0018 .0737 Non—white Male Racti.ua .0283 .1052 Pancreas -.0589 .0184 Non—white a Esophagus .0114 .0176 Larycz .0056 .0601 *ided fl—value based on standard t-test ------- 62 Ovfrall, inclti .on of lung cancer mortality rate as a independent variabi.e did not altar t e siqnif cant results observed betvsen percent surface water and the selected cancer site s.. The regrassion nodel e plo7ed not be consistent across all population strata. Therefore another set of analyses ware perforned with thq counttes stratified by three population strata: counties wtth less than 50,000 population, 50.000—250,000, and sore than 250,000 populatIon.. The results are suanar zed in table iLL Generally, the individual cancer sites showed a pattern for regression coefficients which in eased in size across the population strata (smaller to larger) with the largest population stratun (>250,000) 5howing the greatest nunber of significant associations between the cancer site and percent surface water usage variable (table 1 ) . ------- £3 Table 14: !sr w ted Percent Surface Water Usage Coefficients tth .Value$* from Weighted Regression M 1ysis Stratified by Pcpui.ationr for 346 Study Coimeies. 50,000— <50,000 230,000 >230,000 Sex-race Ceneer Sits B p-vai.zie p—value a p—value hits Males —.0011 .7422 .0005 .8905 .0100 .3153. Large Intestine —.0159 .0611 .0029 .8168 .0669 .0743 —.0024 .6101 -.0005 .9519 .0333 .2516 Larynx .0012 .6426 .0026 .3858 .0107 .0895 Trachea, —.0233 .1686 .0363 .1136 .0391 .3640 Bronchus & Lung Bladder & Other .0026 .4803 .0128 .0001 .0012 .9258 Uri ’7 0rg s AU Mi-i t —.0581 .1076 .1039 .0453 .3317 .003.6 ecp1asns White Fe a1es —.0108 .2861 —.0040 .7231 .0197 .0912 Breast .0091 .321 .0107 .2432 .0512. .0089 i1tip1.e fye1oa .0043 .0331. .0002 .9369 .0018 .1312 Non-white a1ea Rect m .0187 .8577 —.0074 .9113 .0142 .5437 Pancreas .2447 .0001 —.0418 .2973 .0013 .9193 Non—wt2.ita 7enalea soDhagus —.0059 . a.089 .0060 .6951 .0208 .0035 .0136 .0378 .3070 .1689 .3036 .1949 * ,c_ jded ?—‘Talue ase cn z a dard -tast <50,000 ( 272); 30,300—250,300 ( — 62); >230,300 ( — 12) ------- 65 populations of <50,000.. For non—white feiales, e ophaqeal cancer mortality was associated (p= . .00 ) with the water variable in the largest population stzatu (>250,000) with the regessian cceff cients showi q an increasing qradient from the smallest to the largest population stra a. The reverse was true for laryngeal cancer.. The size of the regress±on cceffic±ents decreased vit increasing ccnnty popn.lation. Counties with populat±ons of less than 50,000 bad a siqniftcant azscciae.cn of p=.038 between laryngeal cancer mortality and percent surface water usage. To increase praci on, only co ties having 50 percent or more known water source were chosen for f t her analysis (n1 9). These counties were then stratified by county population size: <50,000 (n=9 ), 50,000—250,000 (n 5), >250,000 (n=10) . . 8cth the reduced set of counties (rt=1L49) and the full county set (n=3 6) showed marked consistency in the regression results when stratified. by county populat ion size (table 1Z,15). ------- 44 Table 15: Estinatad Percent Surface Water Coefficients with p—values from Weighted Regression Analyses Stratified by Pcpulat on for Counties with 50 Percent or More Known Water Sourca.i 50,000— <50,000 250,000 >250,000 Sex-race Canner Site B p_value* B p—value p-value White Male Esophagus —.0042 .3141 —.0019 .6905 .0114 .1611 Large Intestine —.0182 .1016 .0108 .4507 .0803 .0234 Ractun —.0068 .3091 —.0024 .7945 .0387 .li020 La iy x .0010 .7824 .0029 .4319 .0104 .1647 Trachea, —.0315 .2096 .0269 .3046 .0422 .6020 Bronchus & Lung Bladder & Other .0017 .7442 .0163 .0016 .0011 .9287 Urinary Organs fl I4aliguant —.1168 .0258 .1091 .0582 .3352 .0835 Neop lasms White Fensla Ractun —.0029 .6171 .0066 .2292 .0281 .0691 Breast .0110 .3019 .0034 .7324 .0502 .5303 x1tip1e Myeloma .0042 .1145 .0010 .6546 .0024 .2091 Non-white Male Bactun .0241 .7664 .0214 .6004 .0189 .2635 Pancreas .3483 .0011 —.0590 .2166 .001.5 .9341 Non—white Pale Esophagus -.0138 .1671 .0069 .7090 .0217 .0095 Larynx .0238 .0366 .0053 . C55 .O0h 3 .1.590 ,—value based cn acandar - ast —<50,C00 ( 94); 30,000—250,000 ( 45); >250,000 ( 10) ------- 67 As with the full model in white ales, esophagus, large intestine, rectus, larynx, trachea, bronchus and lung and all aliqnant aeoplaz s showed regression coefficients increasing in size across population strata. Uc ever, while in the full cael large intestine and larynx had significant association between the respective cancer sites and the water variable in the largest population stratn ( >250,000), when the nu2ber of counties were reduced, only large intestine shoved an association with the water variable (p=..023). 7iaally, in white ntles- all aal gnant necplaszs prodnced regression coefficients increasing in size over the population strata and had. a päsitive statistically significant association between the co2bined sites and percent surface water usage in two strata: 50,000—250,000 and >250,000-—as had the ode1 with the full set of counties. Par white fe a1es, reduction of the nunber of counties esployed resulted m only rectun shoving both an increasing regression coefficient gradient acoss population strata and an association (p=.069) between the site and percent surface vatar usaqe in the counties with the largest population size, >250,000 3on—vhite rnales showed no significant asscciat cn between rectun and the water 7ar±able ut there was a sire gradient in its rsc ress cn coefficients ‘with the lar;est coefficient ‘being in the county population size of ------- 68 <50,000.. While in pancreatic cancer mortality, the patte:n was si i.1ar to that of the full ode1 (n=3 6): a. statistically significant association between the site and. water variablein the s a1lars±zed counties (<50,000), gon—whita fesales had sinilar results whether the full nuaber o counties (n=346) were used or only those counties with 50 percent or sore known water source (n 1 9) Zsophegeal cancer crtality expressed regression coefiic±ents that increased in size across population strata with the cancer site and water variable hayinc a positive significant association (p=.010) in the largest stratun (>250,000). Is was also true in the full model, lar7nqeal cancer nertality had regression coefficients decreasing .n size froa smallest populated counties to largest with a positive statistically significant asscc ation (p .03 7 ) seen in those counties with popuJ.at±cns of less than 50,000. ------- 69 pc r Since recent studies have suggested a posz ble relationship between the t7pe of water treatnent process, trihalo ethane production and cancer potentia]. (Syncnq ai.,1S75; ifoqan et al..,1976) , the process of treatnent cf pablic ater supplies by chlorination nay be of - i portance. In this study, the process of prechlorination was con .dered a crude surrogate oeasure of possible trihalonethane levels in finished drinking iatar.. Consequently, data was collected for each conannity in each county studied on whether the water supply underwe.nt chlorination and if so, at what phase of the treatnent process the chlorination was added.. n tiaUy the four groups created were: no chlorination, prechicrinaticu (defined as chlor naticn prior to filtration step), post- chlorinatio n (chlorination after filtrat en) and both prechiorination and pcstchlorination .. For analysis purposes, ‘ater undergoing both prechicrination and postchlcrmnation was added to the prechi.ormnaticn qroup he nurber of people ser7ed y public water supplies undergoing rsch:jnatcn ias then &i7ided by the ccunt7 po lation to q ’7e a percent o the t ta county ------- 70 population served by water undergoing prechiorination treatnent. !scause of the possible link of trihalo ethane production with cancer and the relationship between the - organic content in water, chlorination process and tlihalo2ethane prcductian, it is assused that those counties having a larqer proportion of its population served by prechiorirated water would have higher death rates than those served by water undergoing no chlorination process or undergoing poetchionination only. Site—specific cancer iorta.lity rates ware regressed - against percent prachlorinarion and a number o socic- acoso3 c variables for each of the race—se: groups. I su ary of the results are as follows (tables 16,17,18): ------- 7, Table 16: S’i ry of Significant Results 3et een Percent Prech2.oro— nation and Site—, Race-, and Se —specifjc Cancer tort 1ity Rates, 1950—1969, in 346 Stndy Counties. Non-white •C cer Site Male P le Male ‘e a.1a Esophagus NS MS MS S i- Stomach MS MS MS MS Large Intestine NS MS MS MS Rectun S*t si. S* MS Liver & Bii.iaiy Passages MS MS MS MS Pancreas MS NS Si MS Larynx MS MS MS Trachea, Bronchus & Lung MS MS MS MS Breast MS Si- N! NS Prostate MS MS MS MS Xidney MS MS MS MS Bladder & Other Urinary Organs S*t MS MS MS Eodgk(rts Disease MS MS MS MS Ly hosarcona & Raticu1osarco a S t N ! MS MS 1tip1e Mye1a a MS N ! N! MS Leukenia & Alaukaria N! N! MS All Malignant Neoplas MS N! MS p— raiue based on standard t-cast *sjgnj fj t p — <.10 (one—tailed test), un eighted regression ts gnificant p” <.10 (one—tailed test), e ghced regression ------- if a 1. 11: !aci u.d Parcanc ?rsth .1cr nacion 3.p.s.Lou Co. ficiencs and Associued P—values froa .ej c.d aM J.i 4 hcad Rs raasioa Ana .Lys of hi a a1es aM Fs a1.a and SLca—ep.c.tftc Cancer orca1.tcy Races Versus 5.L.c cad Ds rspbic Risic racora for a1ignanc sopLa r:aJ.iy, 1930—1969, tn 346 Co c es.. ita Fenalie 3a r aiaa Regression Z. v. ssiot Ragression 3 p 5 3 p 3 p 1 .0043 .1.72.5 —.0029 .0973 .0003 .3398 .0008 .3047 —.3054 .5009 —. 31.00 .0168 .002.5 .6.457 —.0004 .args tnc.scics .0039 .6334 .0022 .6495 .3052 .5760 .0034 .4924 Racc .0072 .0900 .3141 .0001 .0041. . 3U.2 .3062 .0052 a .0092 - . 3 .1. 7 2 .0020 .4309 .0033 .5961 .0023. .4889 3i1.iaxy Passage. —.0034 .3723 .0032 .3167 —.0002. .9764 —.0000 .9961 t.azyux —.0004 .3722 —.0033 .0028 .0004 .6523 —.3002 .6483 7racnda. .0238 .1.709 .3019 .3419 .0037 .41.38 —.0064 .0060 3ronc ua I —.0005 .4337 —.0002 .3977 .0081 .3972 .02.30 .01.1.9 ? usc.sc. .0059 .3320 .0050 .3223 — — — — .002.3. .7692. .0018 .3134 .0302 .9540 .0002 .3573 •3lsddar & 0tt er .0067 .0393 .0089 .3001 .0023 .3306 .0017 .2131. rinec7 Organs 3od a 3is.aa. —.3032 .2377 —.0019 .1.753 —.0013 .62 .9 —.0025 .0090 ty i oaare a & .001.9 .0998 .3036 .C033 —.0025 .3532 —.3047 .0013 ia gassrco.a 3 1cip1a : .1oza —.002.3 .975 -.3026 .3239 .0005 .3074 .3113 .0973 T. ke.i 4 .0046 .2131 —.0082 .0035 —.0063 .2939 .0035 .i078 A1. eMa *3.1 .0412 .0974 .0032. .3794 .0001 .9958 .0196 .2212 * o_ j4a4 ;— *Lue bassd on acandard :—cssc ------- 73 7 3.* 18: !.d nacs4 ?*r c P .c 1oTin*Cica !ar.sgjo C .fficL.nu and Aaaoc .aM ?—rajuai from 0 .ig e.d W.i hrnd 8agrmton An,Lys.a of 1a.1a. and o -iih1.ee T.nai.i and Sta—sp.eLf Caac.r 1s Licy 2ac V. *os S.lsc:ad 0. O8T*pbic Zisli E ac:ors fo ta.Li ane 3.oplaan or a3.it7, 1950- 1969, in 346 Cn&nci . - 3on—iihi:. Ma.L.. 3—v *i . T. a.1 .s W.imcM .igf t.d 3a a.aion •Sagr,ission R.g ansi o m 3 5 p 5 p 5 p E.apb..ua .0202 .11.92 .0023 .377 .0029 .6631. .0121 .0872 —.1020 .2387 —.0336 .3786 —.0093 .7703 —.0197 .2512 tax8 tne . .0984 .2104 .0239 .5762 .0050 .96f4 .0136 .7599 .001.7 .0835 .0083 .5964 .0127 .5231 .0052 .6941. tivsi 5 —.6148 .6493 —.0032 .776 —.9173. .3982 —.0166 .1.766 3L1i .ry Pa.zs. .0630 .1740 .0003 .0782 .30 0 .3125 .0035 .3461 Lary —.027.6 .2964 —.0028 .3096 .0130 .3950 .0003 .5933. .3197 .3824 —.0013 .9775 —.0600 .4231 —.0.06 .1236 4 3r.ut .0021 .3610 .0009 .5605 .0738 .4459 .0323 .3290 hosca&a —.0162 .8627 —.0521 .2768 — — — — .0555 .2350 .3196 .3786 .0049 .6948 .0021. .7123 31.add.r S 0th. .3204 .6391 .0066 .6872 .0231 .2035 .0140 .2399 U .xy Oranz !odi i a Dis.a.. —.01.14 .2373 —.3060 .2933 .0027 .7061 .0076 .1337 3 .0046 .3276 .0133 .1 969 .0103 .7324 .0023 .393.3 9 . icu1osar oma - - .1oma .0265 .2505 .0084 .3822 —.0090 .4717 —.0049 .5237 Lavkand.a 5 .0540 .2983 .0222 .3312 .0159 .7302 .01.49 .6302 A1 k a All Mll an .0061 .9339 .1432 .3267 .1366 .5769 .0312 .3138 op1aa o—,id.d p — %Lu. aa.d n scandard t— ea ------- 1, for white fe a.].es, nan—white ae.les and non-white fe alas, whether percent prechicrination was significant or snggesti e for any specif±c site depended on whether unweighted or weighted regression analysis was used., However, for white ales, three of the fo*ir sites were sigsificant under both nnveighted and weighted conditions. 2. with nnveighted regression procedures, percent precblo .naticn showed weakly significant or significant positive statistical association with the following cancer sites: in white males, rectun (p.0 O), bladder & other- urinary organs (p=+.000), ly phosarccna & reticulosarcoma (-p .100) and all malignant neoplas s (p=.100); in non- white sales, rectum (p=.08 ); in non—whitafemales, larynx (p=.100). !o positive significant asscci t cn was found in white females. 3,. with weighted regression procedures, percent pr chlarination showed weakly significant or significant positive statistical associations in the folloving sites: white males, rectum (p+. 000), bladder and other urinary organs p.f.0OO), and lymphosarccma & reticulosarcoma (p= .O03): in white females, rectum (p=.005) and breast (p=..01 2 ); in non—white ma.les, pancreas (p=. 07 8) and in non-white females, esophagus {p.0e7). the number of cancer sites that. were significantly associated iith percent prec or natjou were fewer in nunber than as the case with percant surface ------- 75 water usaqe. he substitution of percent prechlorinaticn for percent surface water did not add any new cancer sites to those suspect with percent surface water usage. 3ectu , bladder, lymphosarco a & reticulcsarco a and, a..U aai.ignant neoplazms in white males were positively associated in the successive analyses with both percent surface water usage and. percent prechlorinat1on . Eowever, in white !alas, esophagus, large intestine, larynx and trachea, bronchus & lung were not significantly associated with the predictor variable (percent prechiorination) as they were with the surface water regrassion series. In white fanales, rectum and breast were positively associated with both percent surface water usage nd percent prechlorination when tested successively but with the latter water variable, u.ltiple nyelc a was no longer positively associated with the cancer site. yor non-white ai.es and non—white fe:ales, the sane cancer s±tes showed significance for both water -variables (non—white nales: rectum, pancreas; non-’whitefe ales: esophagus, larynx). 5. the sixty—six regressions (unweighted and weighted) evidenced a greater number of cancer sites as s±guiflcant than could be ex ected by chance alone only for white na.les and white fenales (weighted regressions). 6. only rectal cancer nortality showed any consiztenc7 acrcss race—sal groups. As was also true fc: percent su rface water usage, rectal cancer nortality was ------- 76 significant for ail groups except non-white fe2ales in regression analyses with percent prechicrination as the water variable of interest. The prcc dure used to select cancer sites and secic- econoeic variables for percent surface water usage was repeated to choose the reduced nodel vith percent prechiorination as the water variable of interest. Generally, overall weighted regression analyses on the reduced 20d21 had little i2pact o the regression cceffic .ents and their associated p—va.luc.s as seen with the full cdel (table 19). The exceptions were ultLple eyelc a in white fei ales (B:..0112,p=.10 0 4. !+. 000 ,p..207) and esophagus in non-’ hite females (3:.O1 3 ,p..O87 3- OO2,p 656) ------- 7” Table 19: Es ’ ted Percent Prechiorination Regression Coefficients and Associated P-values fron Weighted na1ysas (reduced de1) of Selected Sex—race, Site—specific Cancer Mortality Rates Versus Selected De ograph c Risk Pactors for Malignant Neoplasn Mortality, 1950—1969, in 346 Coonties. White White Non—white Non-white Males es Males e a1es Cancer Site P P Esophagus —.0020 .6569 .0124 .0001 .0080 .0002 .0065 .7281 Pancreas —.0092 .7138 Breast .0249 .0001 Bladder & .0092 .0001 Other Urinary Organs Ly hosarccna & .0037 .0258 Reticulos arcona Multiple .0012 .2072 Myslona All Malignant .0026 •.8934 Neoplas *two_sided p—value based on standard t—test inclusion criteria: p < .10 in full model, positive direction ------- Por reasons as suggested with percent surface water usage, lar e intestine and rectal cancer 2orta.l ty rates were combined and unwe qhted. and weighted regression analyses of percent prechiorination were performed for all sex—race groups. Only in white males was there a weakly significant positive: association (p=.099) between the water variable and the coabined cancer site (table 20) When lung cancer mortality rates vera included as an independent variable in the reduced, weighted regress ion model, there were no malor change in the results. The addition of the variable into the model did cause sorne change in ly phosarc a& reticulcsarco:a (p=.0267p=.081) for rhite nales (table 21). ------- Table 2 : T vei tcad and Waisftt.d !sgression a1ysss o Psrc.n: Prec 1 rinaci n and C tbined Sites: LarZs I tesc a and Rsctu for All ace-s.ic G a*ps. CA 1C StT ! _________ p. Whiti fa1. .0117 .2466 . .0l0 .09?4 his Pann Ia —.0010 .g245 .0fl94 .1U :Ton Whit. aLa .0730 . 439 .03Z2 .547 : m Whit. Zana.1a —. 22S .8486 . i .16 .353w *Two_sid.d p—value based a scandaxd t-t.st ------- Table 21: Estinated Percent Prechlorination Coefficients and P—values for Cancer S ta by Race—sex for Weighted Regression Analyses (reduced nodal) Including L g Cancer Mortality as a Predictor Variable. Race-sex White Male Site Rectum Bladder & Other Urinary Organs ty hosarcoi a & Reticulos arcoma LU lig .ant Teop 1as s Rec turn Breast Rectum Pancreas Es ouhagus Laryux .0120 .0088 .0031 —.0078 .0074 .0188 .0041 —.0429 —.0042 —.0024 p _value* .0001 .0001 .0807 .6070 .0004 S .0001 • 8323 .1224 .3532 .4767 White Paai.: Non— hita Male Non—white re a1e * j _ jded p—value based on standard t-test ------- 81 When selected organ sites were stratified by size of COllnt7 pcpulation (<50,000, 50,000—250,000, >250.000) there were differences in estimated regress ion coefficients and their associated p—values from the results when the study coun-t es were not stratified by populatict size (table 22). In .vh±te males,, the esophagus had net been positi Tely associated with percent prechlor naticn. owever, when the counties were stratified by population, esophagus was zignif cantly associated (p=.0066) with the water variable in the lowest population stratum (<50,000). also, the estimated regression coefficients had a gradient going from a negative sign in the largest population stratum to a positive sign in the si allest stratum. L±kewise, laryngeal cancer mortality now was positively azsoc ated in those counties w thpopulat ons of <50,000 (p=..015). in estimated regression coefficient gradient was present going from a positi’7e in the s a.Uest sized counties to a negative in the >250,000 population stratum.. Kectum, which had bean positively associated with percent prechi.orinatiofl (unve!qbted and weighted regressicn analyses), showed no statistical asscciation with the water variable with stratification by study county pcpnlat .cn siZe. :n bladder, estimated grassicr. A coefficients increased in sine from 3:_002-,B:.018 with a significant po .t7e azsoc .3 .Ct bet’ean the s te and the ------- 82 water variable for counties with populations of 50,000— 250,000 (p=.055) and >250,000 (p=.022),.. AU. 2ali ant neoplas s which had been weakly significant with unweightéd regression (p= . .097) did notdenonstrate any association when the study counties were stratified by popui.atjon. ifowever, the size of the regression ccefficjents did decrease in size fron =.051 in the saallezt stratu to 3:—..009 in the largest population In white fe .les multiple yelo a and rectun were no longer positively associated with cent prechlorinat on when stratjf ed by population though the latter did show estinated regression coefficients increasing in size across the strata in a positive diecticn . !reast cancer iortality, previously associated with weighted arzalysis , was now sig nificantly associated with the water variable in counties having a population of 50,000-250,000. There was no consistency between unstratified and stratified resu.Lts in non—white males and fe a.les... neither rectum nor pancreas in non—white a.ales nor esophagus and laryni in non—white fenales shoved any association with peroent prechiorination in any of the population strata.. ------- Table 22: Estimated Percent Pr hiorination Coefficients with P—values* from Weighted Regression analyses Stratified by Population for 346 Study Counties. 50,000— <50,000 2.50,000 >250,000 Sex-race Cancer Site p—value p—value p—value White Males Esophagus. .0096 .0066 .0036 .3225 —.0087 .0918 Large Intestine .0032 .7349 .0098 .3791 -.0006 .9896 Rectum .0079 .1271 .0082 .2700 .0150 .4346 I.axy z —.0002 .9410 .0009 .7622 —.0050 .3300 Trachea, .0442 .0148 .0102 .6869 .0004 .9892 Bronchus & Lu ; Bladder & Other .0024 .3586 .0110 .0551 .0183 .0219 Ur{nary Organs All Ma1ig nt .0512 .1890 .0269 .5921 —.0087 .9413 Neup 1as White Fe a1es Rectum .0023 .4616 .0107 .41.51 .0213 .2317 Breast . 3l7 .1110 .0200 .0582 .0220 .3756 1tip1a ye1ona —.0017 .4446 .0018 .3605 —.0005 .6770 Non—white a1es .0149 .6715 .0097 .6312 .0076 .6437 Pancreas —.0307 - .6480 —.0752 .1082 —.0064 .6079 Non—white ?emales Esophagus ‘.0254 .0014 —.0291 .0592 .0013 .8584 Larynx .0024 .7 41 .0041 .1889 —.0016 . 531 * J s 4 dad —val e based on standard t-tast <50,300 (n 273); 50,000—250,000 ( 62); >250,000 (n II) ------- 1qai , for the purpose of i creasing precision, o 1y those ,co ties with 50 per cent or more known iater source vere selected for further analyses. these counties were stratified into three population stratum dependinq on sie and weighted reqIes .cn analyses were done (table 23). ------- Ta Le 23: Escimacad Per e.nt Prachiorination Coefficients with p—values from Weighted Regression Analyses Stratified by Populat±onf far Co tias with 50 Percent or More nown Water Source. 50,000— <50,000 230,000 >230,000 Sex-race C car Site p value* p—value p—value White Male Esophagus .0109 .0203 .0029 .5015 —.0093 .0889 Large Intestine . .0008 .9433 .0134 .2699 .0185 .0855 Rec u .0083 .2747 .0067 .4122 .0190 .4736 Lary .0007 .8341 .0004 .9065 —.0048 .2371 Trachea, .04.48 .0839. .0099 .,258 .0066 .8987 3ronchus & Lung Bladder & Other .0012 .8388 .0086 .0872 .0107 .2376 Urinary Organs All Mali ant .0616 .0547 .0236 .6366 .0164 .6418 Neop 1as tThite Pe a1a Rectun .0059 .3180 .0064 .2044 .0103- .1667 3reast .0189 .0896 .0152 .2079 .0102 .5303 Multiple Nyelona —.0048 .0974 .0005 .7991 —.0001 .9347 Tan—’ jhite Male Recti. .0161 .8588 .0159 .7433 .0024 .3549 Pancreas —.1309 .2330 —.0900 .0974 —.0089 .3546 on— hita ta Esophagus .0306 .0453 —.0333 .0734 —.0021 .6222 La —.0159 .2061 .0018 .3097 —.0039 .1243 * 4 dad —va1ue as ad c standard t—tas z <5o,o0O ( — 4); 30,000—150,000 Cc — 43); >150,000 Cc 10) ------- 86 In white sales, reduction of the number of study counties resulted in large intestine shoving a eakly signi.ficant positive association (p=. 086) with percent prechloriratjon in the larqest population stratun (>250,000). Large intestine had not previously shown any positive association with the water variable. trachea, bronchus & l nq went froa a significant association in the smallest populat cn stratus to a weakly significant association in the stratun (p.015- p=.08 $) when the nusber of counties were reduced.. For bladder, with - reduction of -county nurnbers, the site was now associated with the ‘ater variable only for the stratum (50,000— 250,000, p= .D87). The association with those counties with population-s larger than 250,000 no longer held.. Feduction of county numbers for all. alIgu ant neoplasms did result in the sIte now shoving a positive association of p=.055 in the lowest population ztratu (<50,000).. In white females, results from analyses whether with the full co plement of countIes or the reduced number were consistent. Eovever, breast showed a shift In population stratus.. While under the f nil coapleient of counties the site was assocIated with percent prechiorinatioc in the 21&dle stratum (50,000—250,000), when the number of counties were red iced. the asscciation was f nnd i the sailest strat n (<50,000). ------- cElP 4 r!B ? 17 DISCt7SSIO 1 ------- 87 i ncn—vhjta a1es, .o pcsiti e azzcciatio ias found bet een the zite and the vater v ria 1e in any strata .. In tton—vhit females, a pcsiti e azsociation between esophagus and percent p:echlo:ination was again observed in those counties vith the smallest pop zlaticns. ------- 89 DISC SSICN In assessing the Lnfo ative value of the sti dy’s results, two major problans inherent in an ecological study have to be evaluated: - the quality of the data and the adequacy of the statistical methods The series of unwq .qhtad and eiqhted reg.rassicn analyses and secondary analyses resulted in a nu bar of siqn ficant and sug 3stive asscciatjons between percent surface water usage (public drinking water supplies) and site—s ec fjc cancer ortality rates (1 5O-1 69) as re crted for the 3L 6 study ccunties located in the Ohio Piver Yalley 3asin This was also true when the water va able, perce t surface ats.r usage, was replaced by the siicond variable of int :est, pencent p:echlonination Eoveve:; while the nurnbsr o signt icant associations exceeded the number expected by chance alone (for weighted reqression with percent surface water isaqe) soie positive sites were questionable in terrns of plausibilit7, i.e, trachea, bronchus lung, 17 phosa:co a and :et..cuiosarcc a and nult p1e 7elc a. ?zvicus ex; nta. r s azc , epi e cloqica2. data and ClCC CZ u .-.t7 ZCC i 5GC i tiai att t r. c: ------- go five specific sites: livers kidney, bladder, large intestine and :ectu . Liver and kidney showed no significant association with either unweiqht d or weightzd regression procedures icr any race—sex group. When kidney was grouped wi’nh bladder and other iirinary organs, all race—sex groups except white males showed no statistically s qnificant associations with respect to both pp rc nt surface water usage and percent prechiorinatict. !ladd.er was. highly siqnif cant in white sales for A both percent surface water usage ( :.O06,p.Ol3) and A percent pchi.orinaticn (B:.009,p=+.000) when weighted regression procedures were used... On stratification by population si:e (3 groups), bladder cancer ncrtality was positively as3cc ated with both percent surface water usage and percent pr,chlorinatiot for counties with pcpulaticns of 50,000—250,000 (3:.OIS,p+..000 and A 3:..O11,p=.0551!. n addit on, bladder was also associated wjth the latter ‘dater variable in counties with A populations over 250,000 (!:.018.p . 0 29). estrtctinq the analises to counties with 50 percent or gore kncwn water source did not appreciably change the results. or both percent surface water usage and percent prachlorinatiCfl, the asscc at.On t’wee each of the water variables and bladder •ja fc .ind n those stud7 ccun es b .avir.q ;c u .latio: sizes of 5O,30C2 0,O00. ------- 91 These findinqs a:e not unique ecent epidesicloqical studies have also shown a positive aszoc atncn between bladder cancer and a watar variable thotiqh results are not totally consistent across sex and race. Pace and Harris reported siquificant regression ccefftcients for drinking water p<.05) frog the iz3issippi Piver for uhit males and non vhite females (1975); !uncher (1976) for white nales in counties using the Chic Rtver as thein source of drinking water; and acqan €t al ,(1976) found an association .b tween chlcrcfor levels and bladder cancer c:tality which was weakly suggestive for white females in the egicn V survey (Illinois, :ndiana, !ichigaan, !innasota, Ohio, and Wisconsin) and suggestive or significant for both sexes in tha Nat cnal Organics !eccnr.aisance Etudy. Cantor et al., (1977) looked at the correlatiOn - between cancer 3ortality rates, by site andsex in whites with leyels of ha lc enated eethanes in drin .ing water supplies after ccrrect nq the rates for known or suspected risk factors. 9l dder cancer was posit vel7 correlated in females wtth levels of ncn—chlcrofcrn t ihalcnethaneS in three :eq ons: north, west and scuth. In xales, the cc elation was strong in the northern :ecion an eszent.aliY :src in the other regions. eqa’ ’e5S o whathet perCent urfacs t r usage on :ercent ;rechlcninati i. ‘ a3 useC a tn at9n 7arna .9 c ------- 92 interest, each of these water f .ctors were ocst consistently associat d with large intestine-rectal cancer mortality. Considering percent surface water usage, in white males cancer of the large intastine was weakly asso ated with the w .ter variable wh3n using the weighted regression for the full 31€ connties and after A stratif caticn by population, (B:. 067,p=.07 ) for counties with populations exceeding 250,000. educticn of the number of co mties considered (50 percent or sore known water source) again resulted in counties with the greatest pcpu.lations showing a significant association between percent surface water usageand intestinal cancer orta2.ity rates (3:.OeO,p=..023). Although large intestine cancer ncrtality rates showed neither statistically significant association with ;ercent prechlorinaticn using the full coaple ent of study counties, ncr an associatio affer stratification of the entire study s,t by pcpulation, reduction of the nunber of counties analyzed (50 percent or acre : noin water source) d d show a significa:t relationship between the water variable and the cancar site in the cst heavily populated counties. Also, the :eqression coefficients for both percent surface water and percent prechlorination increase in sire as one cves across tratu : lowest population o h qbest ccpulaticn size. A ain, previcus stzdjez lend suprort to a possibl link betwaan large nes ine ------- 93 cancer mortality and the water var ab1e.. Page and Harris (197!) and 3uncher’s (1976) investigations resulted in significant results for white feaa.les. Hogan’s study (1976) uzinq the OP5 data showed a siqnif cant increase for white fanales Also the site specific cancer iortal ty rats for - white males was significant when weighted regression procedures were uSadm sqicn V data showed siqniftcance fcr white zales when weighting was used in the mere heavily populated counties. Pectal cancer was the site 3ost consistently associated with the water variable in this study: significant for both whits oales and females (weiqhted regression) and non-white nales (unw iqhtad) when percent surface water usage was included in the model. with percent prechlor at on as the water variable of interest, rectal cancer mortality was positively associated with white males (unweighted and us ghtad), white fernales (wa qhtad) and non—white males (unweightsd). Stratif±caticn by county population size showed sc e consistent patterns and in whites implicated the cra heavily pcpula.ted. ccunties(>2 50 , 000 ). !cr either cf the water variables in white males and white fa ales, est ated : zion c i ientS inca as pcpulaticn stratun size i: eaEed. Ic: white fenales the cancer site was weakly sscciatcd with percent su Ce wa a: usage in the cp aticn stratum >250,000 when both the full ------- complement of study cc’ nties were a 1yzad (B.02 0 ,p=.0S1) and when the number of count±es wer reduced to increase pr3c sicn (B:. 02S,p= 069). ks there is with bladder, so is there some consistency in linkinc r cta2. cancer mortality and surface vater as a result of associations found in various studies. Eoqan et aL.,(197E) in the eqion V Survey, fcund an assoc attcn between ctal cancer crtality and chioroforn leve’s when a weighted analysis was used, thouqh rest ictad to white alez when counties were acre heav i populated.- ectal cancer was statistica.ly sjqnif±cantly associated with chioroforu levels ( FS data) for whIte sales and females. owever, results did not seen to vary accordinq to population stratu3. In Cantor’s study (1 77) correlations with lcq—tota.l trihaio athanes of residual values for male and fenale colon cancer rates net study criteria. owever, these statistically significant asscciaticns ‘vera elj inated b7 ‘he •jnclusicn of 10 foreign stock predictor variables in the regression nodal. - pjdenjcloqicallY, colorsctal canca: exhibits a north—south, urban—rural qradient (!e:g,1 7 ), thus suppcrtinc in part, data f:cn this study. Eowever, while the results f: n t i and other jnv s iqaticns p7icusl7 noted sugceet a link hetween the water ia:i ble and colorectal cancer, there a:9 ee ea1 qua1i7 nc factors, ------- 95 sc e of which aay be qeneraljzed to other sites. Because of the possibility of jsdiagncsjs, :isclassification and cther sources data, bias favorable to rectal cancer deaths over colonic cancer deaths is present on death certif caticn (9.rq,19711). This bias increases as the number of true colcaic cancers are found and is greater for wc en than for man. mother factor important to the interpretation of colorectal data is nct only how the daf iticn of colon and rectal cancer is stated but the definition itself is sub act tc change over time. With regard to different definitions of rectal and colonic cancer, the area of ambiguity is from 3 cm.to 19 cm, from the teni nation of the bowel with one—tweith of afl bowel cancers f linq into this region of uncertainty Those beyond 8 cn are epidimiolcg call7 related to colon cancer. Consequently, while izcide:ca rates for the cclcn and rectum are highly ±ntercorrelated and. whIle etiological factors are common to both colon and rectal cancer, there is a second set of rectal cancers of different etioloqy. While combining large jntistjne and rectal cancers mininied the prcbab.l2.ty o: oiases, there are still substantial differences among populations. nother conside: .tiOn is that the isolation f i:di7idual ects o pcsure vania las ‘with the ti 1 ------- qress cn approach i an ncertaj: proc ss. !stinatin reqression coefficients and evaluating statistical significance for individual variables ay depend solely on the other variables included in the equatton. Illustratively, for cclorectal cancers, Eerg and 3urbank (197 ) 1 ave reported that many, if not all, aetals are potential cocarcinocens being capable of depressing the en ynic activitiqs involved in the netabcis of organic carcinogens. Their study showed a significant positive correlation between intestinal cancer and average cad iuii and lead levels . The results showed, at best, only an association between the independent and dependent variables without ccnsideration of the heavy ietals in the cdsl . . Also, cancer of the colon has been found to be highly correlated with ndicatonicf affluence, i.e.., high fat• diet rich in anisal protein and specifically with beef consusptjon {3erq ,197 &;Dressar md :rvinq,1973). Cther vartables inplicated in b wel cancer etiology have been alcohol (s aU iztest ne: a.les and fe a2 .es); cigarettes (colon: females). alcohol, ciqaratte consumption and beer-dr±nkinq data wer nct included in the aodal because no data were available to character .ze county a ffe:ences a onq the variables.. Breast cancer in white fe al s hcwed a ieak.y sianificant asscciatiC: with ;errent iater usage (!:.O1O, . . TQO) and a significant aesociation ijt . pa:cs t ------- 97 prechiorination (B:..013,p=.012) e Eowever, when stratified by population size he results were variable. Stratification of a.Ll 3 counties resulted in a positive assoctaticn in the most h av ly populated counties (3: • 051 ,p=. 009) with percent sur face water usage as the water variable of Interest. 3ut, when stratification on countIes with 50 percent or acre known water source was carried cut,, no association was found for any of the respoctive strata.. When precent prechiorluation was analyzed as the water varIable of interest, breast cancer 3ortal ty showed a weakly siqnificant association in the population strati m, 50,000 —250,000 !: . .020,p.05S) when 3i 6 counties were considered.. Peduction of the number of study counties analyzad showed breast cancer mortality weakly associated with percent prechiorination in the A lowest population stratum, <50,000 ( :.019,p.090). The validity of th.is findinq is questionable. Aside from thc possibili T of a sj nificant result occurring from chance alone, breast cancer is known to be correlated with colon cancer; it Is associated also v th beer drinking’ and with fat and animal prota ccnsumpticn. he last is possibly ex,lained by greater trcgen synthesis both by the body and the ineestinal flora when a rich diet is consu ed Thus beer drirkir , alcohol. ci arett9 s okiug, ±at and animal protain i.nt ks, colon cancer , br aat ca:c : and bladder cancar forn a set 0± hi hly correlated variables ------- 98 whose effects are diff±cnlt to isolate and as potential confoundars, were not controlled in the present stud’ . with aultiple regression technjqu s, it is difficult to adequately isolate the specific effects of intarcorrelated exposure variables - !sophageal cancer mortality rates were s qnificantly associated with percent surface water usage for both white males fp. ,OLL1) and non—white females (p=.050). Stratification by population resulted in similar patterns for both groups.. whether the full complement of c.ounties or the reduced number were used, estimated regression coefficients increased as county population size Lncreased. ?or non-whLte females. the cancer site and water iariable was po tively associated. in the largest populat cn stratum (>250,000) for both the full number 4 (3:.021,p.0O ) and the r ducsd number (E:..022,p_O10) of counties. The guestion may be r i.sed as to the validity of this finding. In white nales, esophageal cancer mortality is correlated with lunc, larynx, colon, rectum and bladder mortality forming an urban zation” complex. sophaqeal and. bladder mortality are also correlated with smoking but to a lesser degree than with urbanization. :n white males, a significant a . sociatiOr. was found between er ent surface watqr usage and all of the highly correlated cancer sites C prising the “ur anizatiCn- smoking’ complex. a. c acl wh c: s c ------- 99 predispcs tc eso haqeal cazc and thus may possibly be a confounding factor in this study, was not controlled. I similar problem exists in interpreting significant results obtained for laryugeal , and trachea, bronchus and lung data: aside on chance, the urbanization complex, possibly a confounding factor in this study was net controlled. flso, the biological plausibility of surface water qualtty as a :is.k factor fcr t. e mentioned cancer sites is not clear. !owever, the lung is the primary excretory organ for a number of the volatile halo.genated compounds. The above cancer sites did not shcw consistency across race-set groupings. Given that the data available on non-whites are not reliable, ‘why only white males and not white females also? Possibly they have different exposure to the water variable and/cr to other factors that may have an interactive/synerqjstjc effect; or there may be a differing biolcg cal rasponse to the agents in question. -. wo other canccr sites were significant: multiple myelcma in white females and lymphcsarccma & reticulosarccra in white males. Cancer mortality : tes for both sites were significantly associated with pencant precblo:i:atic. Cancer mortality rates for multiple myelcma and lymphosarcoma & : ticulc arccma ie:e significant with percer t u:face u aqe ind3r both g ted. ar. Jeiqrt3d :e i analy E ca ce ------- 100 rate for zltiple iyelo a was vea3cly associated with percent prechicrination with weiqhted analysis while the cancer rate for lyaphcsarco a & reticulosarcoma was weakly associated with percent prachlor nat±on under unweighted cond .tions and strongly asscciated ‘with percent prechiorinaticu vtth weighted analysis. These results v re not expected ..nd cannot be explained at present. acvev r, since they were relatively persistent, it sse s wise to include the two sites in further studies. 3riefly, the results f:c this study and ether studies previously mentioned, show significant asscciat onS between percent surface water and/c: p:echlor nation practiceS for sc e cancer sites.. while causality cannot be deterained, an association is present and further studies with part±cular e phasison intestine, rectum and bladder are warranted. owever, interpretaticn of results is made difficult because of p:cbla s already e.ntioned as well as additional prcble s co cn to the type f data available. he question of intracounty variability was not addressed:— even greatly ho o eniouS regions include i t —reqicn yariabiity. I question a.y be raised as to the degree to which areal traits characterize each of the elements comp:iSin the :e iCn. :: Cu: unit of stud.7, the county, :e a:dlesS of in ercCU t7 size vazia ility, contains a numbe: of elated factors. Pach of these — * — ------- 101 factors, not totally indape .dent of th other, nay vary from point to point in the area in a number of ways or ay vay for su.bpcpulations within the county. however, to have some understandinq of the phenomena in a specific place (i.e., county), £t is necessary to ignore these var aticus within the unit of study and proceed on the basis of arsal hcmc eneity. he extant to which the assumption of ntraccunty homoqene±ty is violated and the posstble effect on the conclusions drawn from the data are not known. 1c ain, in ecological s-tudias, the sampling anit is a population or group ratter than an individual. Since ascer tainment of individual risk as determined by individua.l exposure is central to many epidamioligical studies, ecological s’ adLes could yield individual risk only conditional on. each individual within a population having the same exposure. !oweve , in actuality, there is a heterogeneity of exposure. Consequently, the relationship based on average exposure need not reflect the exposure of any individual; populations with identical average exposures may differ markedly in the distribution of exposure levels nd, ignorinq the variation n exposures results in a loss or the deta led ..nfor at.cn necessary to zo o t thE effects of different envircr.:enta.l aqents.. ------- 102 Another problem, specific to this present study was the use of mcrtaljty data rather than incidence data; this use could prcduca spurious correlations if mortality data does not reflect incidence in all areas. lisa, an issue is the adjustment of mortality (or exposure as may be the case) for other etiolc ic aqents:—for most cancers many environmental and non— environmental factors are known or suspected to be etioloqically significant. Adjustment for such variables in eco.loq±cal studies is ha pe.rad by the hiqh deqree of ccnfoundinq, by the fe study units availa 1e for analysis, and by use of data with different frames of reference with respect to time, place, or persons. for example: data availability may be the deciding zsue in determining th unit of study as was the situation in this study. ata collected for purposes other than the specific intent of the researcher may differ not only in the cbaracteri tic of inter st but also in other characteristics; these data aay introduce confounding; other data items may have to be aggregated so that the data set for the unit of study may possess properties that are not matched on individual items in the population. and, different sets c: neede ata are often available with differing eç:ees of areal br a dow:. often then, the situation arises that as the research design increases in conp1e it7, the probability decreases that the individual data sets’ w .ll have suz: c er .y ------- 103 detailed information on the variable of interest.. Of special importance in cancer studies is the latent period between a carcjno enjc stimulus and the development of the disease. The water data are for 1960. Given a general latency period for cancer of 10 to 30 years, the critical time factor is not adequately taken into account. There is in addition the difficulty of temporal variability even within the jndiv daal data sets. The pattern of areal variability may have, and most probably has. underçon chanqe percent snr aca water usage itself has not remained stable nor have the quality and constituents of the water rernained constant. The unit of study, i.e., county, and/or individual data sets may have undergone administrative changes or chanqes in definition. or example, the source of water for each community in this study has not remained static over the 20 year period for which the cancer rates wire calculated and do not reflect earlier (or later) levels ev3n in a relative sense. use, the data were not collected in a standardized manner over differa:t t :e periods, thus peventinq examination cf time trends. Cther questions concern temporal variability with respect to iqratory patterns .it is not known how long the individual resided in the area in which the death was renorted.. Tao, cancer in some :.cns nay be caused by agents having no :elati3nship to any cf t e gza:ti:i€s neasu:ed. ------- 104 Statistically, sultipj.e regression permits a rather sjip listjc type of ad1ust ent for the s ltiple var ab1as. Ccrrelat on and regression tests are oit3n dependent cn the areai. unit chosen,. s Pobinson de cnstrated (1950), cc relatjcn generally increases with the aggregation of data into larger units.. Size of correlations, and even their direction, say change with a change in the unit of study. s was discussed earlier, with any hypothesis eneratjn prccedur s, the probability of Obtaining significant assoc atians by chance alone are hiqh. Turthersore, the nunber of sigrificant results in this study was strongly dc endent on whether or not we ghtinq was used Sose possible explanations for this occurrence have been advanced by Eoaan et al . (1976). Weighted analysis aay tend to give undue esphasis to the nost populated counties.. However, further testing de onstrata that the difference betwefin unweighted and eiqhted analysis can not be attrIbuted solely to the effect of the scat heavily populated counties.. Given the large variability i the weights used, the correlation patterns a onq the var a bles icladed i the nndenly g cdel qht have been significantly altered by the qht nq factor, thereby cha gina the degree of cc1 iea ±t7 present in the data.. ------- 105 Thus, given the nature of ecolcq cal observations, the choice anon alternative in erpretaticns can not be ‘ade solely on the basis of the observational data. The choice of interpretation also depends en the assumptions ada by the researcher and Instified by analogy or the quality of infozmat on available. , thou gh Two other points are i portan ‘ ‘ pravtotis epid iolcgical studies (Page & a:ris,1975; 3unchar,197 ), eiperimental data ( schenbrunmer 8 iller,1945), and theoretical expectatjons inplicate sites which were not found to be significant in this study, kidney and liv ra The finding of no association is not considered suf ic ent eviden for reiectinq an associatic bet’aeefl th predictor variable and kidney and liver site—specific c:tality. Secondly, given t .at a positive statistical association b tween surface water ‘asaqe and sIte—specifiC ortalit7 is not spurious, an association is not quivalant to a causal relationship. lnexplanatiofl does not consist er ly in suggestIng the factors involved in, or even the general fcr of a relationship: It must also include an estinate of the actual paraueterz of an enpiical relationship and. a de cnstrat.Cn that these paraneterS satisfac ri17 account for the v rjaticn in bcdy of act .ia1 d ta SpecificitY is :egui:ed. I z- ati tiCall7 siqnifica:t association can ------- 106 I cn. .7 sugges.... Lud yet, associations derived f:o ecological studies have ep de ioloqjca2. val ie by provtd ng a basis f or further rezearcb, and understanding o the factors involved that ay isad to hypothesis testing studies regardless of the aany limitations and interpretative difficulties. In conclustcn, results ind.icate the relationship of cancer of the large intestin3, rectun and bladder with use of surf ace water and/or prachiorination practices warrants f ther research. The preliminary results do not .p:ovide a basis for drawinq conclusions concernin causal relationships. ------- 107 APPflDIX ------- 2abl,u 21 $t ni tcanC c .ff4 j- .’ .. i d p.. alu.a* of v.j$hC.d 2. rua.io. 2yIia ror ?.rg.nc Sc. W.c.r Usa. a a .S ScL.ct.4 Soc Vutabtts O sn 544. p,ci ic for b44e taJ. .s. i( a r .op1a ortai.iy, 1930-1969, in 346 S 4 Co.. ’4- . !a 1.y’i4 ?o9 s2a— i ’- - . . I in s -ez - : ‘ r Sorfac. 3o — YA4. in A ri- a 3.. a- Squirt 1ot.tg in f*ui- Vicar btta 1.n tiui i1car . fac zrtn t1. SCock faccuxta .009 .o715 4.05 4.01. —.3390 —.0012 .3863 4.10 4.01. 4.01. .0008 .0334 .08*1. .0424 ‘.05 4.01 ‘.05 4.10 .0001 .3244 .1 331. 4.01. 4.Q5 4.01. LLv .4247 ‘.03 .0252 —.0355 4.02. 4.05 —.0001. .002.6 .0092 ‘.10 c.05 ‘.023 .0029 —.0039 .0018 .1628 3ro- es ‘.01 ‘.02. 4.10 ‘.01 4.02. .0010 4.03 Prsscaz. .001 0 —.0238 11*ddtr6 .0005 .0536 .0174 0 sr Ott— —.3003 .0096 .01 ‘.05 .3062 .0004 6 4J .0 4.025 *.ticn le- s .rc J.ttpLm .0002 - ‘.3 .5 .0032 .0168 4.10 .10 — .0179 .:63.5 .96L2 .10 ‘.01 ‘.3 p..4&L *S tied n standard :-CSIC ------- .ab1a 25: 5Li ificaan !. wiQa C .f!i ients and p raLu.I* 01 isiibtsd !.8rtamio Ma .Lyiis f r Pt c e Surfac. Watan Uza . and 5.1.c ed Socio—.conc in Varta LlI Orpa Si .ci1i f r it . 7 1—, a1.i nsnc I.o i.a .sa or aUty, 2950—1969, in 346 S ndy C.,unci.s. # 1oy .4 Popula— _____ $ p1nyad in Snu-dur- tioc Pan Orban ‘ ——— — Sunfac. o — Madian !dura— in t— abi. Maai— Squax . Popu— ‘arsi in 5t. Wat.z bits Inco .. ian ci4n rt facurmn Mil. 1a ion 5 cc fac urin 1.0041 .0295 <.10 <.32. —.6672. —.0004 . 1.626 ‘.01 ‘.3.0 ‘.01. .0010 <.02. .2391 .0670 <.03 <.31 Ltv.r —.3873 —.0006 ‘.10 ‘.325 Lary —. 0001 —.0069 <.01 <.31 .0007 —.3575 —.0003 .0024 —.0330 .01 ‘.05 <.10 ‘. 3.0 <.0 1. .001.0 1.1.571 .0010 ‘.323 ‘.01. <.01. 31 .ddar 6 Othan Ort— nary 0r8an* od ki .0001 a 1 L9 .01.Lt. J .cL 1.. .0036 31 <35 ‘.1.0 6 ii—— ’ — 7 — 00” .1254 .3903 <01 <.05 <.01 <.325 mann t.o— * 0 — .j .d a *V : - .$ ------- 1 (0 Table 26: 5i ifi anc 3a*rssston Co.Ui i t.. and p.v*Jjaaa* f i.i td ?aç .ssia MaL7ata f r Surface W*c.r aage and SeLected Socio-eco E.c Varlablee Organ St sSp.cific for ao-vbits 91.aza ortaLiy, 1950—L969, in 346 Stu4 Counti.s. • yed Po ,.L.— T in ie urban Z : !npLaynd Cancer Surf ace 3oa- “ dian Educe- in L. ri- abLe i— Square !op a— 7or.in in aan- Sit. W .t*t Thi:s Iac . eion cuiu . factirfa iii. lacioe Stock factu .n .0001 i.ct . 036 .1.969 .02 1 .8 4.1 .0 .01. Liver ?ancr.la .1.1.45 -.1.021 ‘.1.0 .3532 —.3957 <.1.0 .0002 <.03 .0057 <.1.0 51ad ’ 8 other Ur .— tat, Orlan. 304 ________ S 3724 .;319 £LL a.Lig— __ •,t <.03 tent : — ,o—sidM p— ni a a .ec sta24ar i :- eit ------- In Table 27; Significenc Reres io Costftci t .s and p—vaLu.a f 3nuai cad sErsasiøe AnaL .in for ?erc.at rf*e. Wat.t Usa , and Selected Socio—econo ic Vsrieb1 Organ Sit. -Specif in for Mow-i,hits la.1.s, MaUgnaz*c ‘.opLaa. MortaLity, 1950—1969, in 346 Study Counties. S !ploy.d PopuLa— 2 Z 2 Median S Enploy.d in Non-dut— tion ?.r Orban 2 2 !nployed Cancer Surface son— Median duca— in Agri— able Mann— Squat. Popu— Por.ign in Menu- Sit . atsr Vain, Intone Uon cultur. fatatiu$ Mile 1atia Stod i f*cturing .0293 c .at Sconecb .0311 .0026 <.10 <.3.0 Large Intestine .0834 e.05 Liver — 1.8068 .0677 6.4012 c.1.3 Otber Uti- nery Orgsne 0053. <.35 Ly boear — c 4 a1nip1a .0012 .0008 <.025 <.3.0 0012 —.0332 .1404 .5432 .2232 <.10 <.023 <.05 <.05 <.10 &L1 !alig- oant Neo— p1a *tvo gided p—value b*aed n standard ;— eet ------- ill. Table 2$: S1 nifie.ant .grssaiou Co.fficieuta and p —valusa* f .ig t.d ft.gr...ion Melyci.. for Percint Surface ‘ ist.r Usa a and Selected Socic—econosic Variables, 0r an Site—Specific fot Whit. Moles, Malignant N.opiaza Mortality, 1950—1969, in 346 Study Counties. S !aploy .d Po7uLe— 2 2 2 Median S Enplnyed in Mon-dur— tion per Urban 2 2 Enployed Surface Mo.— fl.dia Eduea— in Agri- able Man.— square Popu— For.ign in Mine— Sit. Vater Whit. Incoes tion culture facturing eu. lation Stock facturing !.opba$us .0039 .0003 12106 .0010 .0141 .0653 <.03 < .01. <.025 <.01 <.01 <.01 —.4963 —.0007 .4020 <.03 <.01 <.01 Large .0106 .0006 —.0001 .0034 .0211 .0464 .0882 t .uadne <.10 c.10 <.10 <.01 <.03 <.05 <.01 *ectos .0079 .0008 • —.0003 .0017 —.03.74 .0773 .0356 <.023 <.01 <.023 - <.01 4.01. <.01 <.01. lii .tar7 —.3228 —.0003 6 <.025 <.01 Li,.r —.0004 .0421 —.0354 <.01 <.01 <.01 .0042 00”t —.2238 —.0001 .0014 .0139 .0085 ‘.01 <.10 ‘.01 <.01. <.01 <.01 4.10 Trachea, .0234 .0038 —.1.1210 —.0037 .0002 .1335 .1419 3ros s & ‘.023 <.01 <.025 ‘.01 4.10 <.01 <.01 t o n i IrasaC .0009 <.03 .0009 —.0001 .0021 —.0206 .0331 <.01 ‘.10 ‘.05 <.10 <.10 —.0001 .0071 - ‘.10 ‘.1.0 31add .r 6 .0062 .0008 #10000 .0503 Other Un— ‘.025 ‘.01 ‘.05 <.01 ta y Ot ani - - Hodgkin. Disease Lyapbosar .0038 .0005 —.1.794 & lati— <.10 ‘.01. ‘.10 Multiple .1769 —.0004 ‘.10 ‘.05 #.0000 -.0011 Leakasia 6 <.10 <.03 AU Malig— .0754 .0098 3.7716 .0057 .0096 .2360 .7683 ant3e <.01. .01. <.01 <.01. <.023 <.01 <.01 p1an. ?Wo-4i4ed p— ’ a1u* a.sed ou standard t cast. ------- Table 29: Significant Regression Coeffici.nts and p—valu.s* of Weighted Re, rssaion nsly.t* for Percent Surface Water Usage and Selected Socio—,conoaic Variables, Organ Site—Specific for .hir. Y ales, Halignant eopLasa Hortality, 1950—1969, in 346 S rudy Counties. • Epl.oyed Popula— 2 2 Hedian S Eaployed in Non-dur— tion per Urban 2 2 Eaployed Cancer Surface Non— (.dian Educe- in Agri— able Mann— square Popu— Foreign La Menu— Sit. Water Whit. m a cne . tine culture facturing tile lation Stock facturiD4 —.0710 .0050 —.0050 <.10 <.01 <.10 Stoe.ch —.0004 —.3688 —.0003 .1380 <.05 4.01 <.05 4.01 tdg. .0007 —.0001 .0036 —.0176 .0817 Intestine <.023 ‘.03 <.01 4.10 4.01 .0047 .0003 .2690 — .0171 .0326 .0232 <.01 <.10 <.023 <.01 <.01 4.01. 3iliary —.3340 —. 0004 .0310 Passages 4.05 <.01 ‘.023 4 Liver .0345 4.01 Pancreas - Laryan — .0001 —.0045 <.01 <.01 2rachua, .0005 -. 2315 -. 0004 -.0000 .0011. -.0227 -.0212 Iroac s & ‘.01 <.10 <.01 <.10 ‘.01 4.025 <.02.5 Lung Ireast .0093 .0011 .7798 .0005 .0507 ‘.10 <.01 <.01 <.05 4.01 —.0001 4.05 8ladder 8 Other On— - nary Organe godgkin e .0001 —.0000 .0005 ‘.10 <.01 ‘.01 Disease Lynpbnsar- .0002 .0002 — .0007 .0075 c & Rati— <.025 <.01 ‘.025 4.025 culosarene. Multiple .0020 .1003 . +.0000 - .0004 .0065 Hyelo <.10 <.05 <.05 - <.10 <.1.0 Lauk .a 4 .2460 ______ <.05 All Mallg— .0O 3 -.0022 .0081 .2153 usat Nea— <.31 <.01 4.31 <.0 1. plase. r o_tai1.d rvaluu Sa ed on scaulard :—test. ------- 114 Tabia 30 Si ifiGaut Reg . .sioO Co.Ui ienr.* .ad p .L *i* of WeightM Rigruatoft Analysi. for Perceot Siarf.c. Wat. Usa . a*d Sel.ctad Socio—,cono ic Variabi.., Organ Sita—Specific for )01t-iJI%itt Male., Malignant N.eplas* Mortality, 1950—1969, in 346 Stu4y Counties. • p1oy.d ?op i1a- 2 2 M.dian f.ployed in Mon-dur— tion per urban Eapley ed Surfac. Moit— Median !duca— in A zi— able l4snu— square ?rpu— Foreign in Manu— Sit. lar Whit. Incous eton culture facturing nil. lation Stock facturing Esophagna .0024 —2.9799 .1040 <.025 ‘.03. 4.01 ft o.acb .1550 .2533 c.i0 <.10 .0023 .0011 <.10 <.10 liliary Passage. £ .003.3 <. 10 .0001 —10000 .0006 —.0140 .0112 Sron_cbua 6 ‘.023 <.03 ‘.023 <.01 ‘.023 lrwt ProsCats Sledder 6 Oth.r On— nary Organs .0466 Lysphosar- -.0236 <.05 R.ci— <.05 r n1os.rc .0696 ltip1s 0012 —1.1320 ‘.10 <.10 ‘.02.5 All Malig— .0167 - 16.3793 .9117 <. .0 ‘.05 <.31 nant .o— p las n s ‘r-io—cail.d p va1ue Sa.ssd on standard c—east. ------- 115 rabi. 31: Si8nift .axat ReUession Couffici.nts and p values1 of Weighted Mgr*ssion ‘gi*lysis for ?srtent Surface Water aase end S.l.cted Socio—econo ic Variablan, Organ Site-Sp.cilic ?or ‘On—%lhita Tansies, Maii8nanc :eopLa.as Mortality, 1950—1969, in 346 Study Counties. f Eploysd Pop il .a- : 2 ‘edian # j N() -diaL — ‘ion per Orban 2 2 Enployed Cant.r Surface Son— Median Educe- in Agri— able Menu— square Popu . Foreign in Sean- Sit. Water uhits Intone tion culture facturing nil. letion Stock facturing aopha ua .0107 .0337 —.0763 (.05 ‘.01. ‘.01. .1700 .O5 7.3370 —.2442 <.025 4.10 .0012 .1012 ‘.10 <.10 Siliuy —.0249 — 1.3500 0576 ?aaa*$S & 4.10 <.05 ‘.05 Liver Pancreaa .0023 —2.3238 ‘.05 ‘.025 tarynu .0071. <.1.0 Sroncl*us & Lung 3reaat 5.5203 <.05 Kidney 3laddur & —. 0268 .0462 Other 0r — 4.10 nary Organs Eod$kins .0078 Disease <.10 tynphoaax c 4 leti— cuio.arcane iLtipLs Sye ioan .1943 ______ ‘.10 Aleukanie All MeLig— oa.nt Neo— piasnl .rwo— ai1ed ? —uaiue based on st ndiVd t— eSt. ------- 111w Table 32 : Significant Regression Coefficients and p—values 5 of Weighted Regression Analyses (Reduced Model) for Percent Surface Wat.r Usage and Selected Socio-economic Variables, Organ Sits—specific for San—race Groups, Malignant Neoplasa Mortality, 1950—1969, in 346 Study Counties. -I Median Median Educa— Income tion .0047 .0002 —.2434 <.3 ]. <.05 <.01 .0053 .0007 <.02.5 <.01 .0005 —.1476 <.01 <.10 .0084 .0004 .1758 <.01 <.01 <.10 8reast .0250 .0018 <.01 <.01 Employed Popula— Employed in Mon—dur— tion Per in Agri— able Mann— Square culture facturing Mile .0005 .0148 .0712 <.01 <.01 <.01 —.0001 .0035 .0228 .0046 .0833 <.05 ‘.01 <.05 <.05 <.01 —.0001 .0016 .0133 <.01 <.01 <.01 0472 <.01 .0287 4.10 esophagus .0103 <.05 Lary .0047 <.2.0 jo—sided p —uulue based on standard z—tast .0316 —.0684 <.01 <.01 2 Surface Water 2 Urban Pepu— lation 2 Foreign Stock 2 Employed in Menu— facturing S — / Cancer Raca/ Sits White Males Esophagus .0038 .0004 —.2562 <.05 <.01 <.0]. Large .000* .0092 Intestine ‘.01 .t0 .0071 .0009 <.05 <.01 Trachea, Lusg a4der 4 Other Un- nary Organa t.y hosercoma 4 Raticulo— s oan All .1(gnant 8eopl — White Females .0011 <.01 .0288 .0038 —1.1955 <.01 <.0]. <.025 —.0167. .0839 4.01 <.01 .0308 <.01 .0107 4.01 —.1172 <.01 .0810 .0092 —3.387]. <.01 <.01 <.01 .1280 <.01 .2.333 .7711 <.0]. <.0]. — .0003 <.025 —.0034 4.01 —.0059 <.01 .6101 .0010 <.025 <.01 .0743 <.023 .0015 <.10 .0001 <.01 .0000 <.05 .0074 <.0]. • . .oooO .0004 < .025 <.025 Moltiple My e l Non—vhite Males —.0108 .0375 .0140 <.025 <.01 <.10 .0019 <• 10 .0464 <.05 ------- ‘lip Table 33: Sig iftcant Percent 5ur fac. Water Usage Regression Cost ficiants a d p .3.nas* fran Waihce4 Regression Mtalysss (reduced nodul) • Sex—race—sits—specific Cancer Mortality Rates .rsus Selected Soc o-econoed.c Variables Stracifted by Papulatioia 1 for Malignant Meoplas3 Mortality, 1950—1969, in 346 Study Cot ties. # S E 1oyed Papula— 2 2 N.dian Rap loyed in on—dur— tion Per Urban 2 £nployed Surface Median Educa— in Airi— able Ma u— Square Popu— Foreign in Mane- Water logan. tion culture facturing t1a Lation Stock facturing <50,000 —.0042 .0203 .0630 <.05 <.31 <.01 30.000— .0005 .0039 .0987 230,000 <.023 ‘.01 ‘.01 ,z50•000 .0550 <.05 Large totes tins <50,000 .0012 —.0246 .0777 .1351 .0398 <.01 <.01 <.01 ‘.35 ‘.025 se.ooo— .1133 .0962 230,000 ‘.023 ‘.325 .230,000 .0669 .2264 <.10 ‘.10 <50,000 .0008 .2121 ‘.01 ‘.01 .0043 .0919 .0483 50,000- <.05 ‘.01 ‘.10 250.000 ‘250,000 <50,000 —. 1646 .0093 ‘.10 <.05 .0027 50,000- 230,000 ‘250.000 .0107 —.0001 .0016 ‘.10 ‘.025 <.025 trackua. Branches 4 Lung ‘50,000 .0026 —.3024 .1703 —.1860 <.3 1. <.01 <.01 <.01 50,000— .0061 —.0044 —.1341 250,000 <.03. <.01 <.10 ‘230.000 ------- Il Tabi. 33: (cont .n .d) I I Ep1a .d ?ap ga— : Z fl.dian ! joy.d in Son—dur— tion Per Urban : £nplcy.4 S &rfans *dian E4uca— in Ari- abl. anu— Square Popu- Ior,i$n in u W.c.r Inc u cian culture facturin Mile latiou Stack facturtn$ M*LZ (cane’f) lla4dsr & Oth..r Urinary Qrgai ‘ 30,000 .0007 ‘.01 30,000— .0185 .0366 230,000 ‘.0 1 ‘.05 p2.50,000 All MAli ant <50,000 .0044 —.0031 .0366 .3522 .7126 <.01 ‘.01 ‘.01 ‘.31 ‘.31 50,000— .1059 .0116 —5.3330 —.0086 .7204 250,000 ‘.05 <.01 <.025 ‘.01 ‘.01 ‘250,000 .3317 .0326 —10.4942 .0045 .6664 <.01 <.01 <.01 <.10 <.01 W PE ALZ3 Ract <50,000 .0571 <.03 50,000- .0873 250,000 ‘.025 ‘250,000 .0197 .0041 <.10 <.10 3r .at .0011 1.2398 .0013 <.0 ] . <.01 <.01 50,000— .3019 .0610 250,000 <.01 .10 ‘zso,ooo .03U .0066 .0027 ‘.01 ‘.01 ‘.03 )taltiplm .1oaa ‘50,000 .0043 .1681 <.03 <.01 50,000— .0001 —.0003 250,000 - .0000 —.0003 ‘250,000 <.025 <.05 ------- 33: (con tinu.d) t I i — : Mudian Ep1oy in • on—th z ‘ion P .r Crba 2 Surfac. Msdta n duca— in Agri— able a u— Square Fopu— ?or.i*n in M u- 1nco tion cultur, facuring il. 1*tton Stock fscturLng tTE AL ‘50.000 o,o00— 250.000 ‘230,000 Pancreas ‘50,000 .2447 <.01 50.000- 250,000 ‘2.50,000 0 ITE Ft AL Egoplt ag ‘50000 .0276 —.0779 ‘.01 ‘.10 50,000- 250,000 ‘230,000 .0208 —.0921 <.01 ‘.31 ‘50,300 .0136 ‘.35 50,000- 250.000 ‘230,000 tvosjd.d pulu. Sea.d on standard t—Cest ‘<50,000 Co — 27 ); 50.000—230,000 Cu — 62); 250,000 Co — 11) ------- I2 o Table 34: Signif canc Regression Coeifici. ts and p-vslues* of Ua’.ight.d Regression Analysis for Percent Prechloriuacjon and Selected Socio -econo c Vases • Organ Site—specific for S hice aleu, Nalignanc eaplas. ortality, 1950-1.969, in 346 Study Counties. # S E p1oyed Populs- 2 2 2 2 fladtan E 1oy.d in toa—dur— clan Per Urbao 2 Replayed Prechian— lløn— edian Educa— in Agri— able Menti— Square Papu— Foreign is Mann- maRion vhLt. tncoee clan cvlture facturiag tie latian Stock facttarins Esaphagos .0009 .0019 .0719 ‘.01 ‘.10 ‘.01 —. 3871 —.0012 .3907 (.05 .0l (.01 Large Intestine .0007 —.0016 .0023 .0312 .0804 .0453 ‘.05 ‘.10 ‘.023 (.023 (.10 ‘.05 .0072 .0007 —.0006 .0014 -.0213 .1288 .0402 ‘.10 ‘.01 - (.10 ‘.023 ‘.025 ‘.01 c.01 liver 4 Other —. 3890 Itiiaxy Passages ‘.05 Pancreas .0265 —.0330 ‘.01 ‘.05 taxyoz .0005 —.1570 —. 0003 .0017 .0100 ‘.10 ‘.10 c.05 ‘.05 ‘.01 Traab.a. .0058 —1.8231 .0017 .0001 .1731 .141l Irunck . ,a 4 tang ‘.01 ‘.023 ‘.01 ‘.01 ‘.01 ‘.025 Prostate .0010 —.0263 .023 .10 lladd.r 8 Other .0067 .0005 .0007 .0576 Vrinesy Organs .10 .01 .10 .01 ledkios Disease .0003 .0112 .01 .01 Lyepbasarcosa & .0002 —.0032 .0201 lacian ia_rcaea .01 .10 .023 0002 Lsukeeia 8 .0019 .0004 A1suk a .10 .025 aji a3 .ignant .0482 .0077 .0053 .0187 .233.3 .9667 1 eopLasas .io .01 .01 .10 .01 .03. ,— -,. *tvo sided p—value based on standard t—test ------- w ‘able 35: Significant Coefficients aM p—values 5 of Ua v.ighted Ragression Ma slysis for Percent Pranhioriution and Selected Socio—ecooonic Variables, Organ Sits—specilic for White Ts el.s • Malignant eop1asa Mortality, 1950-1969 • in 346 SrMy Counties. I 0 E Loyed Popula— 2 2 Msdiaia £nploy.d in on-dur- tion p.r Urban 2 Epioi.d Pr.chlor- Moe— Median Educa— in Agri— able Mann— square Pop.— Poreign in Menu— mattes White Incoes ties culture facturing mu. litton Stock faccuriug .0044 .0091 4.10 ‘.05 —.6038 —.0004 .1552 <.01 <.10 <.01 Large Intestine .0010 ‘ .01 .3482 .0676 ‘.023 c.01 Liver & Other -.3006 Siliary Passages i .025 Pancreas .0119 ‘.10 —.0001 -.0069 ‘.01 4.01 Trachea, .0006 .0003 .0024 .0319 Srosthus 4 Lungs ‘.01 ‘.10 ‘.10 ‘.01 Sre.az .0001 1.1665 .0001 <.315 ‘.01 ‘.01 3ladd.r & Orher Urinary Organs aodgkins ta.eae .0001 <.10 Ly bo.ercoas & tmticul.oearcoe* - MeiXipl.e Mps3.oss .2 -579 .0096 .05 Lonkesia & Aleukania .0036 —.0023 - .1059 .3676 <.01 <.05 ‘.023 ‘.023 o—jid.d p—’ra3 .u . hued on standard t—ceat ------- Table 36: Significant .re.sicn Coefficients and p—va1ue. of Unv.ight.d Regr.uion Malysia for Percent Prch1or .nstien and Selected Socio-.conosic Variables • Organ Site-specific for on .-vhite Males, Malignant Maoplaa Mortality. 1950—1969, in 346 Stud’, Co tte.. I I Esplayed Pea— Z Median Eaploy.d in Nco—d*ar— non Per Urban 2 E loy*d Precblor Moe- Medi Educe- in Agri- able Mann- Square Papa— Toreign in Mann- Lnar.ian uttjta Incose cion culture factaring 1. 3 ,aticn Stock factu4ng .0023 —2.0832 —.1.582 <.10 ‘.10 ‘.10 Stouach Large Intestine .2436 ‘.10 Rectus .0017 .0049 <.10 ‘.10 Liver & Other 3Lliary Passages Pancreas L ar nz :rach.a. 3ronchus 4 Lung .0002 <.05 Pruscat . .0057 <.10 Zidney 32.adder Other Urinary Organe iaease Ly ho.arcusa 4 p.atjculosarcos. L.uks.ia & Alenkaeda —18.8606 .8856 ‘.10 ‘.10 *tvc iided p— a1u* aaed O, scandard t-teaC ------- Table 37: Si .if ca.nc Coefficientj and p —v*Lusi 5 of t3nv.ight.d Rs reasi Analysis foc Pereest Prechlørinacion and Selected Socio—econenic lariab les, Organ SL:e—specific for Non— whit. Tenai..i, a1ignan: ‘.opLaa Nortality, 1950—1969, in 366 Study Coimnies. # # !nploy.d POpula— 2 2 Median Eçloy.d ja on-dur- tion p .r ban 2 2 £npl.oyed Pr .chlor- . ?on— Median Educe— in Agri— able tenu Square Popi*— Foreign in Mann- insUan vtLite Into .. tion culture facturing ) ls litton Stock factur5.ng Esophagus .0274 <.01 .0306 .0023 ‘.10 ‘.10 Large tntestLAs 8.2762 <.10 .0783 <.05 Liver & Ocher 1.67 1 3 .0642 3iliary Passages <.023 403 Pancreas taxynx .0130 —.1031 .0012 <.10 tra .a, 3roncbus S Lung 3rea.st 6.2308 ‘.10 idngy 3ladd.r & Other .3515 Urinary Organs <.03 EodgkLni Disease .0083 <.05 ty boearco & aticuLos arc on* Meltiple My.lona .0013 —.8109 .0008 <.02.5 ‘.10 <.10 .0012 —.0326 .1399 .5515 .2176 L.uka a .1e <. <.023 <.05 ‘.023 All ai.ignant Neaplaao. *t iaiidad p—value based n stand-axd t—celt ------- ab1 . 31: Significant 2. ression Co.f2ici nta and p_v.lu .a* of Weighted Regression Analysts for ?*rc.nt ?r.chlottn.tion d S.1.ct .d Socio—acononic Variables. Organ—Sits—specific for White Hal.., ‘ aii .ast .optas* Hortality, 1950—1969, in 346 Study Cøimci .s. • 9 £ploy.d ?o u1a— 2 2 2 Hedisa Eploy.d in Hen—dur— tio Per 0rb 2 tnploy.d Pr.cblor— Non— ,dian Educa- in A4ri- able Hasu— Square Po - Foreign in u- macme vhits Inco.. tine cutter. facrerto 14i1. 1atic Stock f.cturing .0003 —.2484 —.0002 .0009 .0179 .0712 <.03. <.01. <.3.0 <.01 c.O1 <.01 —.3242 —. 0009 .4096 —.0267 <.025 <.01 <.01 <.10 Large lacasein. .0006 —.0001 .0034 .0299 .0589 .0804 <.10 <.10 <.01 <.01 <.01 <.02 .0140 .0008 -0000 .0021 —.0156 .0759 .0377 <.01 <.01 ‘.05 <.01 <.02 <.02 <.01 Liv*t & Other —. 3341 —.0003 .0081 3ilisry Psasagn. <.01 <.01 <.10 —.0005 .0117 .0423 —.0353 <.01 <.10 <.01 <.01 larynx . 002 —.2665 —.0001 .0000 .0014 .0182 .0132 ‘.10 ‘.01 <.10 <.01 ‘.01 <.01 <.02.5 Trachea, .0037 —L1318 —.0038 .0002 .1555 .0854 —.1358 8ronchns 4 Uang <.01 ‘.02 <.03. <.10 <.03 . <.05 <.01 3rwt .0009 <.05 Prnstac .0009 —.0001 .0022 —.0215 .0337 <.01 ‘.10 ‘.025 <.05 <.03 .0059 ‘.10 NLadder & Other .0089 .0076 .0507 Ortnary Organs <.01 <.01 . <.01. Rodgkins Disease Lyho.arcoea 8 .0056 .0004 —.1982 .0002 !.ticniOUrcOSa <.01 <.01 <.03 <.10 .1382 .0000 -.0003 .0040 —. 0088 <.01 <.10 <.03 <.10 . <.05 .0000 —.013 .0126 Lneka .a 8 A1auk & <.025 <.023 ‘ .025 All. a1 .ignant .3097 4.4036 3061 .0104 .2951 .8474 R.opl.ag <.01 ‘.01 <.01 <.01 <.31 <.31 .—.— -. - *r.o...,jdd p—va.Luea based on standard :—teat ------- 125 ab1. 39: Si iftcanc P-e rea.ian Coefficients and p_,alues* of W.ignt.d agreseion Analysis for Percent Pr.chlortnation and Selected Socio—.cono c Variable, Organ—Site—specific for Whit. ?enali, , ‘ ali ast !eapl.asa Mortality, 1930—1969, in 346 Study Cow ciea. # I Eaplay.d Popula— 2 2 2 2 Median 1oy.d in oa-dur- cion Per Urban 2 £nploy.d Prechlor- So .- ‘ .dias Educe- in Ari- able Xa *- . Square Popu- Tor,i a in Menu- ination whit, taco.. io. culture facturing Uia lation Stock Lecturing —.0736 .0035 —.0056 ‘.10 <.01 <.05 —.0004 —.33 —.0003 .1837 ‘.03 ‘.025 <.03 <.01 Lar u Intesrias .0007 —.0001 .0037 —.0201 .0847 <.02.5 <.025 <.31 <.05 <.31 .0062 .0002 .2286 —.0138 .0352 .0222 ‘.01 <.10 <.05 <.01 ‘.01 ‘.01 Liver & Other —. 3322 —.0005 .0318 3iliary Pasanges ‘.05 <.31 <.023 Pancreas .0373 —.0145 <.01 <.10 —.0001 —.0051 <.01 <.01 rath. .. .0005 —.26â4 —. 0005 .0012 .0100 —.0260 Sroncbo. & Lung <.01 <.025 <.01 <.01 ‘.05 <.01 Sr.a.t .0130 .0011 .7319 .0006 <.023 • <.01 <.01 <.325 —.0001 <.05 $ladd.r & Other . oo Urin*ry Org Rodgkio. Disease —.0000 .0004 <.03 - <.05 Ly ho.arco$ & .2232 eticu1csarco5a <.03 Melcip I. frelone .0868 .0000 —.0008 ‘.10 <.05 <.01 L.uk a & .0002 .0002 .0000 —.0008 .0092 A1.uk a ‘.023 ‘.05 <.05 ‘.31 ‘.01 jj .0043 — .0021 .0002 .0087 .2230 <.31 <.01 <.10 <.01 ‘.31 tjo—sided —vaju* based on a candard t—cesc ------- Table 40: Significant Regreesion Coefficients and p—values* of Weighted R.gr.seton Ana1ysi for Percent Preeblartascion and Selected Socin—econoede Variables, Qrgan—ei:e—ap.ciftc for Non—white tales, Malignant N.oplaes Morta3.lcy, 1950—1969, in 366 Studp Counties. # Employed ula— 2 2 2 2 Median Employed in Non-dur— tion Per Urban I E loy.d Pr.chlor Non— Median Educa- in Jgri- able Mann- Square Popu- Foreign in Manu- inatio white Imc. tion cultvre facturing Mile latton Stock facturing Esophagus .0024 —3.0423 .1102 (.023 ‘.01 ‘.01 St...ch .1429 .2769 <.1.0 <.10 Large Intestine .0024 .0017 <.10 <.10 Liver 4 Other Siliarp ?weges Pancreas .0003 <.10 .0013 <.10 Trachea, —. 0055 .3139 Sronchus & twig <.10 ‘.023 3rwr .0001 -.0000 .0006 —.0114 .0096 <.05 <.03 <.025 ‘.05 ‘.05 Proetate Kidney Zladdar 4 Other Urinary Org - Hodgkins Disease .0203 Lymphosarcnna & Racicuioearco ma / Ma. ltip le .0013. —I. 1884 .0710 eiusa .10 .025 .10 L ik a & A l.uke . a All Malignant .0170 —16.9206 .9886 .10 .025 .01 *t ,o ided p—valu, based on standard t—cest ------- IZT Table 41: 5Lnific t !.resston Coefficients and p—valu .s of V .tghtad egresiton Analysts for Percinc Pr.cblorinatioe and Selected Socjo—.cononj Variable,, Organ—sita—ipecific for ‘4on- tte Final... ‘tslignanc Neop1as ? rtaUcy. 1950—1969, in 346 Cozmcies. S iEployed Popula— Z Z tadian En 1cv.d in 1o—dur— tion Psr Urban £ployed Prechior— you— edim Educe— in Agri- able anu— Square Papu- Foreign in tanu— tuition uhite tncese tion culture facturing M l . taiion Stock facturing .0131 .0429 —.0629 ‘.1.0 ‘.01 ‘.01 Seoascb .1960 ‘.01 Large Ingeptin . 6.9951 —.2137 ‘.023 ‘.10 Rsctt .0012 .0929 ‘.10 ‘.10 Liver S Other —1.1345 .0435 3tljarv Passages ‘.10 ‘.10 ?ancrea. .3024 2.2409 ‘.35 ‘.02.5 Trachea, Zroncbus 6 Luag 3mc 5.3979 c.05 3ladd.r 6 Other Urinary Organs odgkinu Disease .0076 .10 ty hc.arcoea 4 .1945 leticulosarcoan .10 9z1ttp1 . .01.2.2 .10 T.auk a S £1* uks * All !alignznt *t,o . .ejded —r Lu . based on standard c—test ------- I 3 Tabi. 42: Significant agr.a.ion Coefficients and p_vatu*s* of ¶Jetghtsd Regression Analyses (l .duc.d Model) for Percent Pr.chloriaatjon and Sei.ct.d SocLo—.concuic Variables, Organ Sits—specific for Sex-race Croups. Malignant M.opla Mortality. 1950—1969, in 346 Study Counties. # # Eploy.d PopuLa- 1. .dian Eplayed in ilon-dur- tion per Urban 1. Enploysd S.x-rzcsl Pruchiur- Median Educa- in Agri- able Mann- Square Popu- Foreign to Mann- Carter Site inazioe men .. tin, culture facturiog Mile latin. Stock facturiog Whit. Melsa .0006 -.3C53 .oooo .0182 .0737 4.01 <.01 ‘.01 4.01. cOt Lule .0007 —.0001 .0035 .0303 .0533 .0777 Inte gia . <.01 <.33 <.01 <.01 <.01. <.01 .0124 .0009 -.0002 .0010 -.0146 .0877 .0309 ‘.01 <.01 ‘.10 <.01 <.01 <.01 <.01 .0002 -.3179 -.O 01 .0017 .0174 .0083 <.05 ‘.01 <.31 <.01 <.01 4.35 Trachea., .0038 -1.4635 -.0035 .0001 .1313 -.l25 ) 3roncbua, 4.01 ‘.01 ‘.01 ‘.01 ‘.01. <.01. Iladd.r 6 .0092 .0007 +.0000 .0503 Other Un— 4.01 4.01 <.10 <.01 any Organs Lp phoaareu . & .0037 - .0005 icaticulosarcOsa 4.35 ‘.01 All Malig— .0087 -.3887 -.0064 .0087 .2933 .8294 nant ice.— ‘.01 ‘.01 4.01. <.31 <.01 <.01 p la.i Whit. T..mL.s l.cti .0080 .0003 —.0069 .0433 .01.25 <.03 ‘.023 <.01 <.01 4.01 .0249 .0020 .4462 .0012 4.01 4.01 ‘.01 ‘.01. .0665 .,..0000 -.0003 .0043 4.Q5 ‘.03 ‘.05 <.10 $o ,-.hits Males .0019 .0017 4.01 Xoa- it . Fe.ale a Esophagus .0390 -.591 ter *tuo..gided p alue based an standard t -test ------- Tabl. 43: Si nificanr Percsnt ?rechlortnatton a .s.ion Co.fficianca and p_v*lu.s* fro* Weighted *sgr.eeien ‘ ,nalya.* (reduced nodel) of S.z—Race’-Stte—specifit Cancer corra1ity aces ‘ersia Selected Socio—.cono c Variables Stratified by Popuiaciont for 4alignanc eup1as rta1ity, 1950—1969, in 31.6 Scndy Couutiea. S S ! p1oye4 PopuLa— 2 2 2 .4i !ploy.d in cn—dur— ti*n Per Orban 2 Eploy.d Prechior- (edian !duca- in Art- able A$ri- Square Popu— Foreign in tanu- macion Inc ti culture culture 1. lation Stock faccurin <50,000 .0096 —.0056 .0160 .0593 <.01 <.02 <.0 ]. ‘.02 50,000— .0005 .0041 .0971 250,000 <.0 1. <.01. <.01 ‘250,000 —.0087 .0011 ‘ .31 ‘.10 Laz. lnt tin. <50,000 .0013 —.0269 .0708 .1091 .0663 <.01 ‘.01 <.01 <.10 ‘.01 50,300— .0036 .1133 .0950 250,000 <.10 <.01. <.025 ‘250,000 ‘50,000 .0008 —.0051 .2063 <.01 ‘.10 ‘.01 ‘0 000— .0046 .0907 .0482 20:300 <.023 ‘.01 ‘.10 .250.000 Larynx ‘50,000 —. 1781 .0098 ‘.05 t.323 an .0031 230,000 Z50 000 .0013 ‘.05 Thadtsa, 3r cku. 4 Lung ‘30,000 .0442 .0022 —.0043 . 81 -. 9 6 <.025 <.31 ‘.01 .01 . 1. 50 000— .0061 —2.5817 —.0043 .0838 250,000 <.31 ‘.05 <.01 ‘.01 ‘250.000 ------- 13o TabLa4S: (conrinu.d) I I Eplcyed ?ap La— 2 I Median Enployed La on—thar- tion Per Urban 1 Enploy.4 ?tecbior— Median Educt— La A i— able Agri— Square Popu— Foreign in Mania— 1nca . rto eu1tu e c .4r . . re Mile mUon Scock faccuring U1fl MALZS (cont’d) Iladd.r 8 Other Urinary Organs d O.000 .0007 < .01 30,000— .0110 .0371 250,000 ‘.10 ‘.10 p250 ,000 .0183 .0012 .0650 ‘.025 ‘.05 ‘.025 All Ma.Lignan ‘50,000 .0042 —.0042 .3148 .5118 ‘.01 ‘.01 ‘.01 ‘.025 50,000— - .0103 —5.3939 —.0085 .0317 .3711 250.300 <.01 ‘.025 <.01 ‘.023 <.01 ‘250.000 W Z7Z F tAL25 ‘50,300 50,300— .0123 250,000 ‘.10 l50,00O 3 reast .0010 L.Zt.07 .0013 ‘.01 ‘.01 ‘.01 50,000— .0200 .3020 230,000 ‘.10 ‘.01 250.000 Meld.pls <50.000 .1347 .01 30,300— .0001 250,000 < i D .0000 <.03 ------- 131 Tai 1.+ (conciuu.4) S I E 1a .d ?optal,— Z Z 2 Median E p1oyed in oa—d ar iou Per Urban 2 E.nploy.d Prechior- Median Educe-’ tn Mn- able Agni— Square Papu— Foreign in u— inetien Inc tioa culture culture tie latien Stock Cacuuning 50 -WXtZZ MALES - 2ac: ‘50,000 .0416 <.03 50.000— —.041 3 <.10 ‘2.50,0 0 0 .0241 ‘.0 5 ‘50,000 50,000- 250,000 ‘230,000 50 Z ‘50,000 0234 —. 1 050 <.01 <.025 50,000— —.0291 .0492 Z50, <.10 <.023 p2 30 300 .0612 —. 3336. <.10 <.01 Larynx <30,000 50,000- 250,000 25a.x0 5 t’ o_ajde4 p- a1uu based an standard t—tesc ‘c50,O00 Co —273); 50,000—250,000 (a 62); ‘250,300 (a U) ------- K* • 1 1 y ,•,•• I .. 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