Document KJ1avBQ45JBdMeQVn8X66g85x

NEAll HT wr EHP content ML version o i f hrc s accessible this article i vote pe L310 TA to individuals with disabilities. A fully access s available at http://dx.doi.org/10.1289/ehp 30ible (Secti .1306615. o n 5 0 8 - c o m p l i a n t ) RReesseeaarrcchh Hu Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Liivviinngg NNeeaarr a CChheemmicicaall PPllanntt VacAveg n arai saetrSeoa ians Vaughn Barry, Andrea Winquist, and Kyle Steenland eeSerta ame ve Cor, or Gon USA Rollins School of Public Health, Emory University, Atlanta, Georgia, USA chesoi PFO eedidiim df Da sks nd -- BACKGROUND: Perfluorooctanoic acid (PFOA) is a synthetic chemical ubiquitous in the serum of a ae an] U.S. residents. It causes liver, testicular, and pancreatic tumors in rats. Human studies are sparse. mre com cn ee St vay td ON 5 Sit Bek OBJECTIVE: We examined cancer incidence in Mid-Ohio Valley residents exposed to PFOA in TE oi ep pt mo drinking water due to chemical plant emissions. se i pen ou ARSE | S00 ssSgt METHODS: The cohort consisted of adult community residents who resided in contaminated water te ao me districts or worked at a local chemical plant. Most participated in a 2005-2006 baseline survey in Ee er herd which serum PFOA was measured. We interviewed the cohort in 2008-2011 to obtain further EE medical history. Retrospective yearly PFOA serum concentrations were estimated for each parST, SLTeL o ticipant from 1952 through 2011. Self-reported cancers were validated through medical records and Es rar cancer registry review. We estimated the association between cancer and cumulative PFOA serum wn concentration using proportional hazards models. a pr aape greg, SSE Co 0 RESULTS: Participants (n = 32,254) reported 2,507 validated cancers (21 different cancer types). Btn oY 5 abd pnCMa SCTE rr Estimated cumulative serum PFOA concentrations were positively associated with kidney and tesErr ns |hee h ticular cancer [hazard ratio (HR) = 1.10; 95% CI: 0.98, 1.24 and HR = 1.34; 95% CI: 1.00, 1.79, respectively, for 1-unit increases in ln-transformed serum PFOA]. Categorical analyses also indi- en et a ec mg, Een sl (1009 adBrel Jorgen cated positive trends with increasing exposures for both cancers: for kidney cancer HRs for increas- I LL h Rem rT Fa Or ae ing exposure quartiles were 1.0, 1.23, 1.48, and 1.58 (linear trend test p = 0.18) and for testicular Ae i fae in ich cancer, HRs were 1.0, 1.04, 1.91, 3.17 (linear trend test p = 0.04). CONCLUSIONS: PFOA exposure was associated with kidney and testicular cancer in this population. I r oi n ne JRCReiR n 3 Because this is largely a survivor cohort, findings must be interpreted with caution, especially for highly fatal cancers such as pancreatic and lung cancer. rt VV tt 01. Poll 101 cy St i ot, CITATION: Barry V, Winquist A, Steenland K. 2013. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect TH dg T tg, POPE PFOA andprose andpancrecaatnciercs 121:1313-1318; http://dx.doi.org/10.1289/ehp.1306615 noducton Th ble chins by ehh Sa a H me3a oncE,r a)2 Introduction Perfluorooctanoic acid (PFOA, or C8) is a Chr toma Pp a de hei20 synthetic chemical used since the late 1940s hanaen tm nga oe HO in manufacturing industrial and household Ee tni t, Eo ea e Sw rsfsORhwpaorsg S[o5p3 ASPAoR products (Steenland et al. 2010). It is persis- The biologic mechanisms by which PFOA caused rat tumors, as well as the pertinence of the animal findings to humans, are unclear. PFOA activation of peroxisome proliferator receptors may cause liver tumors plant workers compared with other regional DuPont workers [standardized mortality ratio (SMR) = 181.0, 95% confidence interval (CI): = 93.5, 316.2]. Steenland and Woskie (2012) recently updated this study and reported a significant increase in kidney cancer mortality with increasing estimated cumulative PFOA serum concentrations based on 12 kidney cancer deaths. SMRs (95% CIs) by increasing exposure quartile were 1.07 0(0.92.2858,%,33.C.999I9):),,000.(0(92955,%%3.CC6I2I::)0,0,,111..3.44722)),(,9aa5nn%dd 22C.666I6:. (95% CI: 1.15, 5.24) (trend test p = 0.02). There have been two PFOA-cancer inci- dence studies among general populations: Eriksen et al. (2009) and Bonefeld-Jorgensen et al. (2011). Eriksen et al. (2009) enrolled 57,053 cancer-free Danish adults 50-65 years of age; they measured PFOA plasma concentrations during enrollment and followed participants for approximately 10 years for incident prostate, pancreas, liver, and bladder cancers. Positive associations between PFOA and prostate and pancreatic cancers were reported but were not significant, and no significant linear trends were seen for any of the four cancers. A case-control study of 31 breast cancer cases from the Inuit population (Bonefeld-Jorgensen et al. 2011) reported no relationship between PFOA and breast cancer. The unadjusted odds ratio tent in the environment and has a long human half-life (Lau et al. 2007; Olsen et al. 2007; Sd IOI Ir ha som nd tpn Seals et al. 2011). PFOA is found at low levels in the serum of most people living in IATL A nm en whe Sh Le the United States, with higher levels observed Ey er Th Te eos olnd ON re rs AY in occupationally exposed workers (Calafat Ish In en Ns en EGR abo et al. 2007; Lau et al. 2007). Exposure sources Eo im dsae Pr ON xO in the general population are not well estabkp nh LE ME A Hieror lished, but likely include diet, drinking water, ihbey kde, debe OA bre en ET food packaging, and household products (Lau CELIO. FRO wareportotiendde moetwithfw cancerJesh. One dy Sd oe HehEarUno 1513 et al. 2007). PFOA was reported to induce fo20 00 predmd pen cd Cue SR TL liver, testes, and pancreatic tumors in male ear hs Bnet es EUSUeTa rats over a 2-year period (Biegel et al. 2001). i oso Te i SATstIectoItet However, no evidence was found of hepatocelhts aseyoibia lular, testicular, or pancreatic tumors in male BASS SIESTA, Tt ae SI oc monkeys exposed to PFOA for 26 weeks and redfo 90dasafc xo (Butaboll cores with nce PFOA expire, SmeAtment(Creat Courof Wood observed for 90 days after exposure (Butenhoff rl ado Ton S00, Sr be oe et al. 2002). Exposure levels used in the aniSe bed ire A i hus mal studies were higher than human levels typically seen from drinking water or occupa- yh rd ar my lyondon Tle El pn tional exposure. Because of PFOA's potential talon FT o A, Lt pT for environmental persistence, long human olerand pone vnc hers fing DuPont Wishigion Workplan Com. Ie sageeyoe to pr half-life, and possible toxicity, there is rising Coc otwhmge bessr obaed ted nthe preoesLotonua dsyo, mma concern about whether it might be associated with human cancers (U.S. Environmental Pye air oe Protection Agency 2005, 2006). in rats (Kennedy et al. 2004), and also in rats, PFOA-induced increases in serum estradiol levels (Biegel et al. 2001) may have caused testicular tumor growth. It is not known if these processes are relevant to human cancer (DeWitt et al. 2009; Koeffler 2003; Suchanek et al. 2002). Most previous human studies of the association between PFOA and cancer have been mortality studies of occupationally exposed workers with few cancer deaths. One study followed workers employed at a Minnesota PFOA production plant between 1947 and 1997 (Lundin et al. 2009). These investigators reported some evidence of positive trends for prostate and pancreatic cancer across job categories with increasing PFOA exposure, but estimates were based on only 16 and 13 deaths, respectively. A second mortality study followed workers who had been employed at any time between 1948 and 2002 at the West Virginia DuPont Washington Works plant considered in the present study (Leonard et al. 2008). These authors reported that kidney cancer mortality was almost doubled among (OR) was 1.07 (95% CI: 0.88, 1.31). PFOA levels are typically low and widespread in general populations. The DuPont chemical plant in Washington, West Virginia, began using PFOA in its manufacturing process in 1951. The plant released PFOA into the Ohio River Address correspondence to V. Barry, Departments of Epidemiology and Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd. NE, Mailstop 1518-002-2BB, Atlanta, GA 30322 USA. Telephone: (612) 669-9098. E-mail: vbarry@emory.edu Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1306615). This work was supported by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, West Virginia) between DuPont and Plaintiffs, which resulted from releases of the chemical perfluorooctanoic acid (PFOA, or C8) into drinking water. Funds are administered by an agency that reports to the court. Our work and conclusions are independent of either party to the lawsuit. The authors declare they have no actual or potential competing financial interests. Received: 5 February 2013; Accepted: 29 August 2013; Advance Publication: 5 September 2013; Final Publication: 1 December 2013. tees a Environmental Health Perspectives t VOLUME 121 | NUMBER 11-12 | November-December 2013 31313 EExxhhiibbiitt 33551122 State of Minnesota v. 3M Co., Court File No. 27-CV-10-28862 351122..000011 Barry et al. and air beginning in the 1950s, peaking in Using the C8 Health Project cohort in and 74% of the participants 20 years of the 1990s, and decreasing emissions after combination with a DuPont worker cohort, age consented to further contact by the C8 2001. PFOA emitted from the plant entered the C8 Science Panel conducted subsequent Science Panel. Of these, 82% participated the groundwater, which was the public drinking water source. In 2001, residents living near the plant adr de filed a class action lawsuit alleging health dam- de PROM named dining age due to PFOA-contaminated drinking interviews in 2008-2011 to gather disease incidence data. Cancer incidence results from Methods that investigation are reported here. Methods in one or two surveys during 2008-2011. The C8 Health Project participants who completed at least one subsequent survey did not tankeron differ significantly from the original adult ne oe emery C8 Health Project participants with respect Ro SA SCA T water. A pretrial settlement required DuPont to provide funding for an independent community health study called the C8 Health Project (C8 Health Project 2012; Frisbee et al. 2009), and also resulted in the creation of the benNout S80 pd ey Data sources and study participants. The C8 Health Project surveyed 69,030 persons between August 2005 and August 2006. Participants were eligible if they lived, worked, or attended school for 1 year in one 2BelTy ome to age, sex, education, water district, or PFOA serum concentrations measured during 2005-2006. They reported demographic information, health-related behaviors, and medical history. In addition, we obtained a C8 Science Panel (C8 Science Panel 2012), of six contaminated water districts near the list of DuPont workers who formed a cohort rd ently which was tasked with determining whether tthheerree wwaass aa pprroobbaabbllee lliinnkk bbeettwweeeenn PPFFOOAA aanndd disease in the community living near the plant. The C8 Health Project surveyed Mid- nthe ad p8lbteh plant between 1950 and 3 December 2004. PPaarrttiicciippaannttss rreeppoorrtteedd ddeemmooggrraapphhiicc aanndd hheeaalltthh characteristics and an extensive residential history. Serum was collected for PFOA mea- that was originally constructed for a mor- taalliittyy ssttuuddyy ((LLeeoonnaarrdd eext aall.. 22000088;; SStteeeennllaanndd and Woskie 2012). This DuPont cohort was formed by DuPont and included 6,026 work- Ohio Valley residents in 2005-2006. The surements. The estimated C8 Health Project ers who were employed at the Washington, pho ri tih BATiain survey collected medical history and also measured serum PFOA concentrations. The median serum PFOA concentration in this population was 28 ng/mL in 2005-2006, participation rate was high (81% among current residents 20 years of age) (Frisbee et al. 2009). A detailed study description has been published previously (Frisbee et al. 2009). des sTm West Virginia, plant for 1 day between 1 January 1948 and 31 December 2002. Of these, we interviewed 4,391 workers, including 1,890 who were also enrolled in the C8 compared with 4 ng/mL in the United States overall (Calafat et al. 2007; Steenland et al. 2009). The C8 Science Panel sought to enroll adult C8 Health Project participants in subsequent surveys to study disease incidence, pa he Health Project. Figure 1 shows how the analysis cohort was compiled. The analysis included 32,254 persons 20 years of age, who participated "66991,02300ppuarrtciciippaanttsseevnorotlleedd (gust205 August206 in the C8 Health Project (August 2005-August 2006) 6,026 workers in original Dupont cohort -- v in at least one subsequent survey and had exposure estimates. ttoo ppAaalrrltiipcciaipprtaaittceei,ptatoontmmsaagctaccvhhe ppineerfrossoormnnaaelldiincnfofoonrrsmmeana.-t tion to state cancer registries, and to release m`meeddiiccaall rreeccoorrddss ttoo ssttuuddyy ppeerrssoonnnneell.. MMedeidcicaall 54,457 participants were 20 years of age [re 40,145 consented to subsequent surveys resin 32,712 completed at ee least one subsequent survey py (August 2008-April 2010 aannddl/oorr MMaayy22001100--MMaayy 22001111)) Smmen 28,560 participants had no evidence of working dese at Dupont el 4,391 workers completed at least 1 survey (August 2008-April 2010 anndd/oor MMaayy2200%10-May 2L0l11) || eres | 3,713 workers had retrospective PFOA nes es | exposure estimates meinen| (1,890 participated in the C8 Health Zar Project, whereas 1,823 were only in the Dupont cohort) records were protected in accordance with the Health Insurance Portability and Accountability Act (HIPAA) regulation. The ttyAo HESmpl Be study was approved by the Emory University IE Institutional Review Board. IE PFOA estimates. Cumulative PFOA serum concentration estimates were calculated rs etrospen ctivelyfoforr m each comy munity ppaertieci- pant for each year of life beginning in 1952 or the participant's birth year, whichever was preSt e va most recent, through 2011. Estimation proroo dMLEm pi o cedure details have been published previously Sih pire (Shin et al. 2011a, 2011b). Estimates were bbasea doons nhihsie tsotorird iccaallrreeggiioonnaallddaartaa iinncclluuddiinngg tthhee tems PFOA amounts emitted by the DuPont facili BE ity, wind patterns, river flow, and groundvot: l Ep im ksoEloe water flow. Exposure estimates took into account each participant's reported residential repeatan history, drinking-w ater source, tap-water con- Ee api we, sumption, workplace water consumption, and a PFOA absorption, distribution, metabo- AOR bond lism, and excretion model. 28,541 had retrospective The exposure estimates for participants PFOA exposure estimates who had ever worked at the DuPont plant took into account occupational exposure they may have received at their specific TI. Figure 1. Cohort enrollment. i1314 32,254 in analysis cohort job. Estimated serum levels over time for workers in different plant jobs were based Spadn re bt on over 2,000 PFOA serum measurements taken over time from workers (Woskie et al. Saintes 2012). These estimates were used to create a br39 nen es volume 121 | number 11-12 | November-December 2013 Environmental Health Perspectives 351122..0002 940A and cancer isk among adults posed 1 POR BH PFOA and cancer risk among adults exposed to PFOA boone mari rime ru ds foe PFOA cisions), whichever was i, by 10 3d 20 yer in onder 10 comer job-exposure matrix to estimate serum levels first PFOA emissions), whichever was later, by 10 and 20 years in order to consider a fddoerpawerotmrkpeenrtsas.aAcArfrfotsesretteimmmpplemlooinyyemmdeeinfnfntetereennntddteejddos,,bcesxx.appnood-- dtdoeeaactthahanagcgeeer ((diiffiaddgeecnceoeaassisesedda)),g,wewh,ihlcaichshteevsvueerrrcvecaaymmaeegfefi,irso.tr. casccaueusnseeaddrbiobysyeiexnxppowoshsuuircrehe ffcuuarrnthhceeerrriicnnotuthhledepahpsaatsv.te. HbHeeeerrnee macs det co 85 per Foch se ws sed fo svi oe port me ed mi sure estimates decayed at a rate of 18% per Each model was adjusted for time-varying we report the models that lagged cumulative neha rcime eof 30m snaking mcssehen TROY rm omaB10nyo We year based on a presumed half-life of 3.5 years smoking, time-varying alcohol consump- PFOA serum concentration by 10 years. We crm 300 Tomace en on se doc Sea hp Lh mt eh ery 1 (Olsen et al. 2007). These estimates were then tion, sex, education, and 5-year birth year also ran models limited to community resi- rsd ciel Joc fom peta We hed oped ids Jens ah 4 sk wk po combined with estimated serum levels from period. We checked the proportional-hazards dents who did not work at the plant in order elon pon osm dig. mon oh bby doin 5 cor wih rls eb residential exposure to contaminated drinking assumption for each model by including an to explore whether results were driven by the NC mcd combined soot] or te mecion and and n. Hh PRON capo cernbyewode water. We estimated combined residential exposure age interaction, and found no vio- high PFOA exposure experienced by workers. goin pour fo STS BHD) oa erpaoadrmsmt ont otplw oted coy and occupational exposure for 3,713 (84%) lation of the proportional-hazards assumption Quartile cut points were recalculated for every frCeoomn ds ov cofrmation proces. Oeonnpityppoe eo 035, ie scom ionigo Pains we shed ieso ci FOR rncient in prs of the interviewed workers. Cancer data and confirmation process. Participants were asked "Have you ever been (all interaction p-values > 0.05). Our primary exposure metric was cumula- tive PFOA serum concentration (in nanograms ReSults cancer and population subgroup model. Results Eo oro ot heh plo ile ero choot Demographic chapters Tb1dei told by a doctor or other health professional per milliliter-years), which was calculated as the Demographic characteristics. Table 1 dis- tv daor sleys oy ofl er conctn BoSpdo ifor n 3390e pr that you had cancer or a malignancy of any sum of all yearly serum concentration estimates plays descriptive data for the 32,254 partici- Ld pms port oe a opi ion se coc hv. Pain tong 5p kind?" Participants reported the cancer type up to a given age. We considered models that pants. Participants were, on average, 53 years gto Thos spars Peel he) ogof ome FOR oe foe oh ne wi and their age at diagnosis. Those reporting included the natural log of cumulative PFOA of age at the time of their final survey, with a ol em canonxcoon le ans gh oh dn oe cancer were asked to allow us to review their serum concentration as a continuous variable male participants slightly older than female ids or A led cos wena md me cn. (54 0 33 se) Mo papas medical records. For all self-reported cancers, (a test for trend), and models that included cat- (54 years vs. 52 years). Most participants i dons lion mel. ae vk cole cio. ver of ie re nd we omy we sought diagnosis validation though medi- egorical variables for cumulative serum concen- were of white race and were community ao Oro Voit ion gale, Te oo smi com ds Hors pecon hc woke cal chart review or Ohio/West Virginia state tration quartiles. The log of cumulative serum residents. Eleven percent had ever worked at gnmake onset es he he Sabot pk Fonpanswee cancer registry matching. concentration consistently fit better than the the DuPont plant. Female participants were Eicee gyva bin es snl sae tuscon. re Hy oe so og con The Ohio state cancer registry was begun linear untransformed cumulative serum con- more likely to have some college education in 1992 and the Nn Vr ag momento ado te Lake mon hn vk Fans (5 o women in 1992 and the West Virginia registry in centration [based on the Akaike information than were male participants (36% of women 50a 1s pois whe gard vain AOL primal bc bs. hl Fags wh Pd 1993. If a participant who self-reported a criterion (AIC)], presumably because log trans- vs. 29% of men). Participants who had ever ac nd i of er om ed oe fy wah fe Dunpone we ne ily cancer type was found in either of the state formation diminished the influence of relatively worked at the DuPont plant were more likely es on wt pre os weve Bh or en, dS mo cc cancer registries to have that cancer, we con- sparse data with very high cumulative exposure. to be male and older at the time of interview med he newinrg the rg We Te aon fo amd compart ahpaop to Dsie firmed their cancer using the registry. We The interpretation of the log cumulative expo- compared with participants without DuPont ee Err also sought medical records for participants sure coefficient is that an increase of one unit work experience (80% vs. 42% and 59 vs. i ne cnr nd wh cen oocame cotals + ae 53veh uwusshttooo-rddepooso0sro.te.SdSoocmmaenepcepararartnicdtipwianhctoswicwohhpnoosraeernepntpoeodrtrttfeseoddr roriisfskklo((gRRRcRu))omofufleatcivcoeommepxappraoreseuddrwewirtiethhsuttlthhsoosisnee wawitirhtehloaotninveee 52 yPPeaarrtsaicoifpraagnett)sw.whihoohchaaddwiworoprkkeeaddaatntthheteplpalsannet rete ond Tn he ei co. Shed ot ar end et BOR cr nck 2005-3000 cancer were not identified in the registries unit less. We also tested for a linear trend in had higher PFOA serum levels in 2005-2006 Be mg (possibly due to living out of state or receiv- log RRs in categorical analyses by assigning the and also had higher estimated annual PFOA gro 9% i poecto st nd ngs oa cope panop ing a cancer diagnosis prior to 1992) and in midpoint to each quartile and conducting a serum levels compared with participants who OE adi mic cots toed nc ion obTo RR ss sed bepo Te 3 Op these cases, we used their medical records to weighted linear regression of the log RRs on never worked at the plant (Table 2). On aver- omi ored onc Nelld rls mip. apione 5 oon confirm self-reported cancer. Medical records these midpoints. age, each participant contributed 33 follow-up em datos he prune Ch pinseu ecedonon 1 He 0 eofredre, were received from doctors the participant Quartile cut points were calculated among years after 20 years of age but estimated serum rl we Wat eB he ome: HOR sos comer ocd er 10 reported were relevant to the specific condi- the cumulative PFOA serum concentration levels were low prior to 1980. od gl fo iyo ps so poh a dg onan poe 589 diffe tion and ranged from primary care physician estimates for the cancer-specific cases at diag- Participants reported 3,589 different eit login rd i om home thcome mlth cancer doo covering 31 cet ren records to oncologist records. We confirmed nosis time. We also considered models that cancer diagnoses covering 21 cancer types; oe Fewi suns orton eid cola FOR sn conenton 350 con gmswee ind 0050, cancers if there was sufficient information in lagged cumulative PFOA serum concentration 2,507 cancer diagnoses were validated (70%). ad To lomo end ode tmmheeenncrteiicooonnrdoo.ffTcchaainnsccienerrfoddrimiaagagntniooosnisissc,,outtrlrdeeaaittnmmceleunndttses TTaabblle1e1. DDmemagorgarapphhiicc cchhaarracatcetrisotricssooff ccoohhoorrtt n=(n = 2322,52504)) bbyy ccoommmmaunintityy aanndd ooccccuuppaattiioonnasl ggrroouuppss CD std Conny Ie ee DirDeeciseseiaevseseds,,,NNIiCinnDtthh-R9Re[veIivnsitsieioornnn,a, tCCilolininvaiilccCaalllMaMsosidofdiicicafitsciaoitnoiononf CD50 (tor Comer to ity oe ihn Cems bod (ICD-9-CM) (National Center for Health [n (%) or mean SD]. Characteristic ETnrtieretcoohronrt (n = 32,254) Cogn Community group (n = 28,541) Geieigon Occupational group (n = 3,713) Ses 2006) ond S10 aie IBS) I5 Statistics 2006)] and ICD-10 [International Sex SilCoDei nts n hd oe uss names 2s Statistical Classification of Diseases and Related Male 14,894 (46.2) 11,939 (41.8) 2,955 (79.6) i tn osi tos Jt RR] Health Problems, 10th Revision (World Health OGrpriiiomn 92 ccooeion een ne. byeee sume omws sae Organization 1992)] codes, or specific cancer- or tumor-descriptive characteristics. Seitet mobos Oo mn nes 0% we Taian ds wweereeSrtraeetsitssrteiiccetaeddl tatoonvaavllayilsididsaa.tteOeddpurprirmimmaarairynycaacnananclecyresrses.s. nPnPooacrtvtaviacalilipiddraaanttteestddwwwhwehioreorerereeceepxpxoccorllriututeddedede3pddfafrcrcoaoaamnnmccenethrhreetthhtssaapptetecWcswiifafaiisccs Female Race/ethnicitya White, non-Hispanic uo ihcht Other Educationb SiLHoegimgshshetschhcoahtnooeohgloiegorhrccsecnhretoifsoicltateeooff uequhivoalelnceyG(nGEEOyD)) Some college 17,360 (53.8) 31,144 (97.4) 815 (2.6) ames) 3,063 (9.5) 29107) 12,971 (40.2) 0s2028 10,522 (32.6) 16,602 (58.2) 27,860 (97.6) 681 (2.4) aws08 3,026 (10.6) TASMIO 11,706 (41.0) swim 9,441 (33.1) 758 (20.4) 3,284 (96.1) 134 (3.9) Fo 37 (1.0) 1285000) 1,265 (34.1) een 1,081 (29.1) cemod od moby Rens "Ene dam ime cancer model and thus did not contribute any Bachelor or higher 5,694 (17.7) 4,366 (15.3) 1,328 (35.8) iimneto moak sion odd HLenrLie --- wr moEme ou person-time to the model. A proportional hazards regression model a co pl hen Treen was run for each cancer type with the can- m Lyme on orl wdeelel Ee w1m y e=m mone, cer as the outcome, time-varying cumulative PFOA serum concentration as the indepen- en vac ed pe he te, omens Wess sews dent variable, and age as the time scale. J Participants were followed from the age of re en he vn sree aya pe25 ns fm cote 20 years or age in 1952 (the year after the Mean age at final interview (years) Mean year of birth Type of participant Community only Worker only Community and worker 53.0 15.6 1957 15.6 28,541 (88.5) 1,823 (5.7) 1,890 (5.9) 52.2 15.6 1958 15.6 28,541 (100.0) -- -- 59.3 14.1 1951 14.1 -- 1,823 (49.1) 1,890 (50.9) GED, General Education Development test. aRace/ethnicity information was missing for 295 participants (all from the occupational group). bEducation information was missing for 4 participants (2 from the community group and 2 from the occupational group). in Hdl st pc +von 21 112 Horn December2073 131s Environmental Health Perspectives volume 121 | number 11-12 | November-December 2013 1315 35122..00003 a saryetal. Barry et al. Table 3 show de amber of crc digs suv i rsd wi an end Table 3 seo. praporional based Table 3 shows the number of cancer diag- cancer risk increased with an increase in the Table 5 reports proportional hazards ass pane, te mbes wih ciel Io of imate culate FRO ru con. model rls or lee cance sing en noses reported, the number with a received log of estimated cumulative PFOA serum con- model results for selected cancers using esti- A AR PnSe Sil medical record or state cancer registry entry, centration (Table 4); this association was sta- mated cumulative PFOA serum concentra- Ind th mamber sre. We abies tcl Soa ony forctu canes on quale. Eimared ARsfo Kidney and the number validated. We obtained a tistically significant only for testicular cancer tion quartiles. Estimated RRs for kidney record te vi fo 39% of slporcd ot+h105 ewl. To hl rs (HIG) ances cbt anesgn ined record to review for 88% of self-reported at the p = 0.05 level. The hazard ratios (HRs) cancer and testicular cancer generally increased noe.Rego fr emt lode 08 9% Co rs Yon rae ih morrow es gotowhi dt Tor cancers. Reasons for nonvalidation included and 95% CIs were similar between models monotonically across quartiles, while the pat- ep Ep le seg ett his ong RR vor por a bog living in a different state, having a cancer where exposure was unlagged, models where tern across thyroid cancer quartiles was less rior hecites of dh fo css es tps wo ged 1 Js nd mol Sonn. VAs or vc wend 1sof prior to the existence of the two cancer regis- exposure was lagged 10 years, and models consistent. p-Values for linear trend tests of i or ing vy cont for medic econ whos xpos ws aged 30 years Goals og ve rio actos quartsof anoged tries, or failing to consent for medical record where exposure was lagged 20 years (results log rate ratios across quartiles of unlagged review Tot sofa ltrpory edcance ox how. The mo entaldhigshly exposes (wingCapoetonmeid vrveavraiieedwrb.byyTichcaeeanncacdececrrussritat.cey. BBorrfeeaassesttl,,f-bbrlelaapddoddreetrer,,dkkciidadnnneceyey,r, nbbeeotttteesrrhoffoworrnuu).nnlTlaahggeggeemddeoexdxpepolosssugurerneececroaomlmlpyapfraitreesddligwwhiitttlhhy pepoxoipinnottsss,u, raaennsdd(uiinnsvivneerrgsseeexvvpaarroiisaaunnrcceee cwwaeetiieggghhotirinnyggiminnida4- Bo Sg EA AEN rR et lnA ft prostate, thyroid, colorectal, lung, leukemia, 10- and 20-year lagged exposures, as measured no-intercept linear regression model) were nd phoma cance were mse Hy10. by ALC. Ress don ll slfvponed 035,01a5n:d 0f.td0d4, oes, amd and lymphoma cancers were more likely to by AIC. Results based on all self-reported 0.25, 0.18, and 0.04 for thyroid, kidney, and Ee onion Soper oy oes Seer ee emt Aer 2 ie br ont ee AOC To ri be confirmed compared with other cancer cancer cases were similar to estimates based testicular cancers, respectively. The p-values ype. Ceniel comer had a ow vldaron oh saicioseodly (dnxoshowsn). or hyo, deyand tc an ed types. Cervical cancer had a low validation on validated cases only (data not shown). for thyroid, kidney, and testicular cancer trend rartatee,,ppoossssiibbllyydduueettoopparatrtiicciippaannttssmmisisiinntteerrpprreett- TThhee iinnccrreeaassee iinn tteessttiiccuullaarr aanndd kkiiddnneeyy ccaanncceerr tetsetstsswwitithh aa 1100--yyeeaarr llaagg wweerree 00..5577,, 00..3344,, aanndd pel aott he Como a 1 St Feet Wok ocd uals O03. VA eo ep ta ing abnormal pap smear results. Cancer was risk by increasing log of estimated cumula- 0.02. When stratified by occupational status, nee olen vied i Duont wore pr. tt PEON sri, operation was ion. comated Ksfo hyod concer mead more often validated in DuPont worker par- tive PFOA serum concentration was stron- estimated RRs for thyroid cancer increased pans compre with oma siden 1 1 coms dens ompacd ith mones qo uis moog Dent ticipants compared with community residents ger in community residents compared with monotonically across quartiles among DuPont mee wed Duns 736 69%) ular wore be ppl Nt, woes bat di rt mc: monatonicly who never worked at DuPont (75% vs. 69%) DuPont workers (see Supplemental Material, workers, but did not increase monotonically a appear iad Tule SB le SB, Hower th tain bowen or An un an Dantes oe (see Supplemental Material, Table S1). Table S2). However, the association between for kidney cancer among DuPont workers (see parcswom atociion, Til4 ipod inte 1b and PFON was poe SulomtdaTaol t53 essfo Exposure-outcome associations. Table 4 thyroid cancer risk and PFOA was positive Supplemental Material, Table S3). Results for shows rsd roporonl hands model ind sgnhcam in Dulot workrs bu no the wakes chor ar tedb low spe shows adjusted proportional hazards model and significant in DuPont workers but not the worker cohort are limited by low sample evi fotexh cesa bused an valdte omni, reskin (os Supplemenral io or conof eeSs. results for each cancer type based on validated community residents (see Supplemental size for cancers of interest. ml Thy, ep and esi a, Tob 53 Seams hh ats 00 crn cases only. Thyroid, kidney, and testicular Material, Table S2). Because thyroid cancer is more common Tol Mesrn smee OA mg concnnminnishoor 0n-2s78 in omepn,epneeop elE cing de enmTecRh: Table 2. Measured and estimated PFOA exposure concentrations (ng/mL) in the cohort (n = 32,254). in women, perhaps reflecting different mechanisms from men, we ran separate analyses for Eo VEGI men and women (34 aod 74 con rape Cohort Median (range) men and women (24 and 74 cases, respec- essere E08 Tre. Rahs wre sie in ch group Measured PFOA serum level in 2005-2006 tively). Results were similar in each group ee 20247 aor how. Community (n = 28,541) 24.2 (0.25-4,752) firs i "Sig analys We conducsievd- Worker (n = 1,881)a EstimatedsualFOAserum vel Estimated annual PFOA serum levelb CCoommemiutniyty ({n1+=22885,54411)) edward wesaew Worker (n = 3,713) 112.7 (0.25-22,412) 1J9A.4A(2R.8E-9S,2I1T7) 174.4 (5.2-3,683) si ET FrweS ManWeT BTE wLd oo nowy ave eg in or working aWorkers who did not participate in the C8 Health Project did not have serum levels measured (n = 1,823) and other workers were missing measurements (n = 9). bCommunity residents were followed for an average of 32 years, and prt rt marcato ve di workers were followed for an average of 38 years. (data not shown). ORO ae ecrlal Seseennnssiittviivviiittyy aannnaaahllyynssee.ss.. WWWeee clloooonokkdeeuddc tbbeadcckkse vat ecaacchh ppaarrttiicciippaanntt'ss rreessiiddeennttiiaall hhiissttoorryy aanndd eessttii-- mated the time when each participant was first known to have begun living or working in one of the six contaminated water districts, Tbe Nerf ge sodpincoc cs ongcont22o50 Caimuidinnghporidor ttihmae sWaedhecnacch opnesseors Table 3. Number of reported and validateda primary cancer cases among the cohort (n = 32,254). excluding prior time. We then considered survival models that started each person's To raids ene eg ees No. reported (had a time on this "qualifying date," excluding years IN ebm eae befor hat dv. Thsans sued in No. medical record reviewed No. validated before that date. These analyses resulted in coe rus papel) ITS igh lspasontome and lig fewer Cancer reported or a cancer registry entry) [n (%)] slightly less person-time and slightly fewer So TW i TIGHT cance cass han original anaes: again Bladder 115 115 111 (96.5) cancer cases than original analyses; again, a 5 5 3067) ree resims i epored ress HR - " Brain 33 Bfreatst 6=08 Cervical 383 Ee) am a TEED nd eatscancerwere 106 55% Ci Colorectal 311 Esophagus 21 or El iw JE 552113953.Ci 09% 1.20. and Kidney 124 pee 5 i By 13705 099,190foragpeo Leukemia 79 e 7) lativeexposure in relation to thyroid, kidney, 31 23 (69.7) results were similar to reported results. HRs o60u0 5w81e(95n.6) foforraa 11--uunniitt iinnccrreeaassee iinn lInn--ttrraannssfoformrmeeddccuummuu-- 245 22 (5.7) lative exposure in relation to thyroid, kidney, 297 19 276 (88.7) 15 (71.4) and testicular cancers were 1.06 (95% CI: 117 113 (91.1) 0.92, 1.23), 1.12 (95% CI: 0.99, 1.26), and 71 69 (87.3) 1.37 (95% CI: 0.99, 1.90) for unlagged expo- he i i 88 sre nd 102 05% CI: 087. 139, 170 Liver 18 15 10 (55.6) sures, and 1.02 (95% CI: 0.87, 1.19), 1.10 = 2 HER Cao. 120, nd 131 05% Cl Lung 133 em i L288 035180 frcapone ed 10 yun. Lymphoma 164 Melanoma 519 124 113 (85.0) (95% CI: 0.98, 1.24), and 1.31 (95% CI: 158 142 (86.6) 0.95, 1.81) for exposures lagged by 10 years. 414 245 (47.2) Oral 35 oSo n a &$ Sf8a9y Dyiesccuismsaidonocutonsbem eed Ovarian 87 fre Ed 5 BID miei FRO apo a cle Pancreatic 35 Prostate 515 Sore F Sia So ampaou nofigcss apo10 Soft tissue 25 34 20 (57.1) Discussion 65 31 43 (49.4) 26 (74.3) We estimated associations between estimated 476 458 (88.9) cumulative PFOA exposures and incident can- 19 17 (68.0) cers among a group of individuals exposed to frery 5 i E109 DEON trou dlwiironrsoglo he Stomach 29 24 12 (41.4) PFOA through drinking water or work at the fed 2 5 S688 lolDuos chamic plan. oie aso Testicular Tbhyre oid ferns si forkidney, testicular, and thyroid cancer. Uterine Tm awe as 2s po Te wend for Total 32 -98 225 3,589b 21 19 (59.4) 297 8a7 (8,8.8) 173 105 (46.7) 3,146 2,507c (69.9) aValidated cases were limited to participants who reported the cancer and were subsequently confirmed either by en edetme Hogsa ee eg Ly Ghee is cnstnt with 4 rious Ohio/West Virginia cancer registry or medical record review; participants reported whether a doctor had ever told amhahad cancera agar of nyin, hse 483 cancrsworsel upd 22picpunssme DuPont worker mortality analysis, which them they had a cancer or malignancy of any kind. bThese 3,589 cancers were self-reported by 3,292 participants; some ee ees ee oi ie iim ooo participants reported more than one cancer type. cThese 2,507 cancers are among 2,361 participants. local DuPont chemical plant. Positive associa- titoionnssbebettwweeeenn PPFFOOAAaannddccaa ncen rwwec rereefefoouurnndd for kidney, testicular, and thyroid cancer. The positive exposure-response trend for kidney cancer is consistent with a previous DuPont worker mortality analysis, which indicated a positive exposure-response trend 11331166 o121a e112 Nemes December 2013 + Ens HtePespen cives volume 121 | number 11-12 | November-December 2013 Environmental Health Perspectives 33551122..00000044 PPFFOOAA aanndd ccaanncceer skrisk aammoonngg aadduullttss eexxppoosseed 0to PPFFOOAA H for Kine cancer deaths Sunland and. paricipants from bo coors were lve at sobors, asocatons wish PFOA. may be for kidney cancer deaths (Steenland and Woke 3012), Out finadr aih nnaggse the time of thi meric i 3008-2011. bisedsows he mulprifcor hiyghly Woskie 2012). Our findings are also in agree- me ihn ogc dy of ncn 1 pole ths ome puch on ke ci cots nd rk ment with an ecological study of incident Cover rs meto Pl ROMtxo posrs Kiy cancer exes wouhd nok hve bm ances omsGoQutucehsnTudttybg cancer rates in relation to PFOA exposure os beeen 1996 and 3005 in bok Oh nrolldor mtnicued becuse they ded errs wih cin, On te ies bande levels between 1996 and 2005 in five Ohio and ighe West Vieni counics (Vieira before 2009, given thas th 3.yeae sarsvl sicoou]cbebpiasetdwoy fnromsthe and eight West Virginia counties (Vieira S00 2013), which eluded some cancers rte for Kidney cance based an 003-2008 nll i 3 proportionate numberof highly et al. 2013), which included some cancers Singrcdamong rica nthe prone SEER (Sureiiance Epidemiology and xpotaeuspdaciadmshce edy diagnosed among participants in the present cudy opel; Thyrepo asigna End Resa das was oly 70% (aconal + This sy hsscversl othe Kain. study population. They reported a significant Posie aacbetwaeeniKidnoey cannes Canes niu 2012). Tncones, cancers PFOA was cuimad individually for cach positive association between kidney cancer $d he ov igh cima PFOA rm vit ow fly aes, such 2 thyrord and yr of cach prdcpanc ie bated on thei and the two highest estimated PFOA serum xpos categories, iadheldoy,was teil cance wowkd ot bc ped to elfported sesdencial toys DuPont exposure categories. Finally, the kidney was Fert sn bce es wing cvs, be ing fom he sud core. I cancer PFOA cin panand FOA sir: of a priori interest because studies using rats, ie are bn nd Ghana avs wil HE Pores were re cy Yon dogo mbt. amen mice, hamsters, rabbits, and chickens have Shown tht PFfsdObA mainly inthe 1 de before thy cobeanuvolldedin our ion model. There i Hcl misclaificion shown that PFOA is distributed mainly in the Kadneys, ve, and serum (a cal 305: kidneys, liver, and serum (Han et al. 2005; Kennedyct, 3004; Last 2007, Tal HRs 95% C1) for he fof ogg smd cums ROA sre concertos on Kennedy et al. 2004; Lau et al. 2007). Reichs cance was of 4 rior ners, Lana ok Deconmn- 250 Testicular cancer was of a priori interest cae PFOA ho be ho cst oot om Tm because PFOA has been shown to induce tes- sas omer in le ts Ge a 00D) Cee Gt ERG ps WAG pe ticular tumors in male rats (Biegel et al. 2001) an are adil production oTg RERIE ow g wwe 07 and also to increase estradiol production in male rvs, which may increcsicuar To Mois om omemim on in male rats, which may increase testicular ttuummoorrrriisskk ((BBiiceggeellcett aal.l. 22000011).). IInntthheececcoollooggii-- lyperbymVieensad3. GOL, Gove % ompmim a omemiw 0m cal study performed by Vieira et al. (2013), imaicd PFOcouwer rposisvdly Goal @ 0mp@iD Im omemim on estimated PFOA exposures were positively Saced vith ti ams er none Eczroms Wo Smomim om omenmim om associated with testicular cancer. As noted ovecas included i he cologil dy {57 imhmom om memim om above, cases included in the ecological study Sold veply viviecocddog. {22 Semin lp tems i would have partly overlapped with cases diag- nose2d in ouor estuKdyipopurlaotieon. pos `ooffaanTna FoasGoss ouFcriaks tniKoowolnado wgsb,bleeetdc twwgeeee,ei nsnthPhiPea FrFreeOOot aAAreeaai nnn0d6doto trhheyp3yrron oo6riitdds "ances fom permeaof asurael 0 ompmim oe omenim om cancer from experimental studies of animals or erations tuofdhareman popula; Di 8 omni om omemie 08 or observational studies of human popula- Tins. Hower, thesi denetht TFON Posi n lwomim 0m omemim on tions. However, there is evidence that PFOA cited whl cddrt:nrommo algr rnh4ye7., SPoonee @| Oommbpsaiime aoum oopmeewwiimm oowm eni pom is associated with incident nonmalignant thy- roid disease in this population (Winquist and aland 201). Tomato vo imimim om imemim ow Steenland 2012). Ws tonfmed slfceported, cancers 1s LooeEmos mmm We confirmed self-reported cancers tt hroh ughsr sttaatto eeccaanu ncceerrrgergeigsh isttrryy mmaattcchhiinngg aanndd medical record review. Our acer alka: pono hrege s o rr oe EEPl or ork medical record review. Our cancer valida- titioonn rraatteessffoorrbrberaesats,t, pprorstaote,lsluuntngg,,aaanntddmemele,ala-- ee nts re hn pros St ht ep nsatodumdiicae,sc,assnuucggeggresessattriiennggsimtthhiaaltatrbbtrroeeaatsshtt,o, spperroionsstpaetre,e,vi1aonudds lluunng canncceerrss are ttyppiicaallly rreeporrted acccuu-- ars wheres ree nce and pina rately, whereas rectal cancer and melanoma oF th kin maybe seporid es scarey 1 Asp A of the skin may be reported less accurately (Bergmann cal. 1998 Savio cel2011). {o0pOs noe"or ol en ontsi o (Bergmann et al. 1998; Stavrou et al. 2011). WC ied to vid dee prsbypoy. SSO Wiinnggse seterlifle-drefptoo-ratrevdoeciadcpsaestehsoseosrofef"tp"ccroeoollboodlnne"m" aasnnbddy"gr"rreeocctutaalp"l"- oe ool one ce Stat, oy owe? pew) Oorde? Duted Oaed platplo' cancer as "colorectal" cancer cases. Similarly, wwee ddiiddnnoott eevvaalluusatteennoonn-meelalnaomnaossmkkiain canncceerraassaann outccoommeeaanndd lliimmitteedd mmeellaannoomma proo utsn sh to lh cases to participants confirmed for melanoma. Community cohort participants Ths U1 100 INOBAZ 109 IOI 008 003 Community cohort participants PRrRiitr c intheCB Hooe k Prof, and ths Te 100 R J vt HJ it T Fo e ion pe sneer (n = 30,431) had to be alive in 2004-2005 to participate in the C8 Health Project, and thus inbeSigbiclondwioownciomnme G5 810 dwis sos vows oo 0s to be eligible for inclusion in our commu- dnweiinetdyreencnooohorothariitvnn.eWtsthhooeebreCCkea88rlicHHvoeeehaoailnrtlth2p0PPa0rrr4otoi-jcej2icpe0ta0n((51t11s,808w0b28h3e)o) ind ne sud. Norris, ae en or ee Sr eed did not have to be alive in 2004-2005 to be participants from both cohorts were alive at the time of their interview in 2008-2011. It is possible that some potentially eligible kidney cancer cases would not have been enrolled or interviewed because they died before 2005, given that the 5-year survival rate for kidney cancer based on 2002-2008 SEER (Surveillance Epidemiology and End Results) data was only 70% (National Cancer Institute 2012). In contrast, cancers with low fatality rates, such as thyroid and testicular cancer, would not be expected to be missing from the study cohort. If cancer cases with higher exposure were more likely to die before they could be enrolled in our cohort, associations with PFOA may be biased toward the null, particularly for highly fatal cancers like pancreatic cancer and lung cancer; consequently our results must be interpreted with caution. On the other hand, associations could be biased away from the null if a disproportionate number of highly exposed cancer cases participated in the study. This study has several other limitations. PFOA was estimated individually for each year of each participant's life based on their self-reported residential history, DuPont PFOA emission patterns, and a PFOA absorption, distribution, metabolism, and excretion model. There is likely misclassification Table 4. HRs (95% CIs) for the effect of logged estimated cumulative PFOA serum concentration on cancer risk in the cohort (n = 32,254). Cancera No. of casesb No lag HR (95% CI)c p-Value 10-year lag HR (95% CI)c p-Value Bladder 105 1.00 (0.89, 1.12) 0.98 0.98 (0.88, 1.10) 0.77 BBgrrreaeaiansstt 5=5197 0910..4191340((008..88849,,, 111...500100))1 000..04s53 010..9093631((0008..78898,,, 010..94919))) 00o..70m03 Cervical 22 0.89 (0.63, 1.24) 0.48 0.98 (0.69, 1.38) 0.90 Colorectal 264 0.99 (0.92, 1.07) 0.84 0.99 (0.92, 1.07) 0.77 Esophagus 15 0.96 (0.70, 1.32) 0.82 0.97 (0.72, 1.31) 0.84 Kidney 105 1.10 (0.98, 1.24) 0.10 1.09 (0.97, 1.21) 0.15 Leukemia 66 1.01 (0.87, 1.18) 0.88 1.02 (0.88, 1.18) 0.80 ULLuivnSegr 1100898 08008..87(830((007..87483,,, 111...020030))) 00[..20335 pLLyimlwapnhioommna.a 11E%3l6 111.00001100(08081.92,1.,111.0.11922))) 0o0.s8s8 Melanoma 241 1.00 (0.92, 1.09) 0.97 0008..9722400((008..184,13,,111...002846))) 00I..2167 00.9988 0(08.888,, 11..1100)) 0o.7n8 11.00441(009.966.,11..1133)) 00.3x0 Oral 18 0.89 (0.65, 1.22) 0.46 0.66 (0.43, 1.02) 0.06 Ovarian 43 0.95 (0.76, 1.19) 0.64 0.90 (0.69, 1.16) 0.42 Pancreatic 24 1.00 (0.78, 1.29) 0.99 0.96 (0.75, 1.22) 0.72 Samah Prostate Soft tissue Stomach 2 ombsne an wnosia 446 0.99 (0.93, 1.04) 0.63 0.99 (0.94, 1.05) 0.80 15 0.75 (0.51, 1.10) 0.14 0.72 (0.48, 1.09) 0.12 12 0.72 (0.45, 1.14) 0.16 0.77 (0.49, 1.22) 0.27 Testicular 17 1.34 (1.00, 1.79) 0.05 1.28 (0.95, 1.73) 0.10 rUTehteryrrioinnidee 20108336 111..0015501((0009..99115.,,1112..220060)) 0005..25803 0901..9901940((008..58869,,, 111...121505))) 000..69354 nainAgg.,pttriiommpeeo--rvvtaiarorynyiainnlgghsaaizlccaoorhdhosollreccogonnressusumsmpiotpnitioomnn,o,sdseeexlxw,eedaduscuracutanitoifonon,r, eaaanncddshstctrraaantticfeieedrd;bebyayc55h--yymeeoaardrpepalerwiriooaddsoaofdf jbiuistrtthheydyeefaoarrr;;titmmimeee-bvbaeergygaiannngoatstmaaoggkee-. LL Loreen ov mas ni on s ny rf 4 MONS overt 20 years if the person's 20th birthday was in 1952 or later, otherwise time began at the age the person was in 1952; time ended at the age of cancer diagnosis, age at the last follow-up survey, or age on 31 December 2011, whichever came ccfpiPrusestr.uubnNntiutomoffboleogrgeoseftstciimamnaatcteeeddr cccuaumsmuelusalatuitsivveeedPPFinFOOtAhAsesterrerugumrmecscosnoicnoecnnetmnrtoardtaietiolonn(i.(e(n.,sgn/gmolLm)..issing data for any of the model's covariates). Table 5. HRs (95% CIs) by PFOA quartilea for thyroid, kidney, and testicular cancer cases among the cohort (n = 32,254). CCyanmceerr ces No. of casesb fleencel Quartile 1 (reference) _ QQuuaarttiilee?2 Quusatrtieled3 QOuuanrtiileed4 pet p-Valuec pp-Vlaalue'd Kidney N"ogpla,g 1W0S5 1100-yyeeaxr alagg 110055 11.000 11.2330(00.720,127.1)7) 11.4488(00.8844, 22.6600) 11.5588(00.8888, 22.8844) 00.1B8 00.1100 11.0000 00.99O(0.5S3, 11.85) 11.696(09.930, 3.307) 11.4830(0%.726,629.6)9) O0.3H4 00.1155 Testes No lag 17 1.00 1.04 (0.26, 4.22) 1.91 (0.47, 7.75) 3.17 (0.75, 13.45) 0.04 0.05 Mas 510 18GNIM w0N2 HOSIM 05 02 10-year lag 17 Thyroid No lag 86 1.00 0.87 (0.15, 4.88) 1.08 (0.20, 5.90) 2.36 (0.41, 13.65) 0.02 0.10 1.00 1.54 (0.77, 3.12) 1.48 (0.74, 2.93) 1.73 (0.85, 3.54) 0.25 0.20 10-year lag 86 1.00 2.06 (0.93, 4.56) 2.02 (0.90, 4.52) 1.51 (0.67, 3.39) 0.57 0.65 aQuartiles were defined by the estimated cumulative PFOA serum concentration among the thyroid, kidney, or testicular es eesea ohce i cancer cases at the time of cancer diagnosis. bA proportional hazards regression model was run for each cancer; LE casa etefor evn amie, sani con) Corum, se stn,rd Sr each model was adjusted for time-varying smoking, time-varying alcohol consumption, sex, education, and stratified by included in the study. Nevertheless, because oficin cbraniog prov ponders of difficulties in obtaining proxy respondents fofor decdeceeaasesded ttargeettccoohhoorrtt mmeemmberbsaeatt rtGiimsme oF nscrvion in 2008201 most of he of interview in 2008-2011, most of the 5-year period of birth year. Time began at age 20 years if the person's 20th birthday was in 1952 or later; otherwise time began at the age the person was in 1952; time ended at the age of cancer diagnosis, age at the last follow-up survey, or P= Sottee ht Sent et 5apg-YVeualoluuneeDsswewcaeeemrebcceaarll3cc1uulslaattt2ee0dd1u1us,siwinnhggiecexhxpepovoessruurcreaemcceaattfeeirggsootr.rycyTpm-VHidaplOuoeinSistsfoa4rnldinienaevrerrtrsseenYvdaAtreTiasTtnicenetWhweeeiligoghghitrniangtgeinrnaa8tionoso-a-ticnurtoecsrescepqptutablraitnkileeaasr; S$eson att oe eH on retoro e k regression model. dp-Value is from the continuous log estimated cumulative PFOA serum concentration models. viHeo hPerspl ectives +vn121 a 112 amberOc 202 1317 Environmental Health Perspectives volume 121 | number 11-12 | November-December 2013 1317 33551122..00000055 || saryBarry etalet al. i pore pon ge 0] Nat. Sr Ty in exposure estimates, although we did find arin lad) | mim nriyhes susstiit Bad good agreement between model-predicted and Bot 0sSo mg Heet, Sn measured serum levels in 2005-2006 among Ch Heh os pic hol Seema rE the C8 Health Project participants who had pitting wan RE I never worked at the DuPont plant (r = 0.67) (Shin st 2011). Michtfcion old SASRmERMI IEE, pe (Shin et al. 2011b). Misclassification could oe tw i nity Sl rns ThE cause bias if it was differential according to i sveono evil Noung TE SS Te uR tp the outcomes evaluated. Nondifferential misasicaion mor lly co rou in bie CLIO BEI es, Bwn snp classification is more likely to result in bias Toward th mul than sway fom th mul bu Are EI & es vr toward the null than away from the null, but Tomo ng Seiatd 4 ALRSTI MLScr mS rt mes W SS e SE R, not always (Armstrong 1998; Steenland et al. 2000). Also, the cancer validation process was mpl ay ohs mho opr co ey hens SSME implemented only for those who self-reported b brinrginadesc mmidseo sl on JR L SE L a cancer. There could have been participants who had a history of cancer but did not report ie Howes, potential miscsificaion of (ay S SEIE S MANS oa tfrs nes nr its it. However, potential misclassification of a mats wold hv lr pL 8SF ET cases as noncases would have a smaller impact Bor oven sw ono NIN. on the analysis than misclassification of nonGbi e mo baf came ST IS IM SATO cases as cases because the number of cases misisons dy ol rs Dt i , h classified as noncases is likely small relative to el ame ron, Sa AS the total number of noncases. Conclusion ames IER Conclusion Fetes on FON sof ome bs SE PETTITTE | ey yr Previous research on PFOA and cancer has pms std Se ae a ko Sd bmm eeenntsp,rimmmoorarratilalyilittryyes`stsrttiucudtdeiieedss toooff amniamkelewalowreoxkrpekeerrrissa Tm, WEAR with occupational exposure, and community lio oplaions wih lon aque le, PUREpEy | ERT Cn studies of populations with low exposure lev- lelss.aind hbuumeann studniegs hhaavvee.bneenalimd itedbbyy T m m S PTTy S SE R -- R Re B In small numbers of cancer cases. The present study estimated RRs of incident cancers in Sm com WO opr TELA | BEng association with cumulative PFOA exposure in a large community with a range of expo- inalg communy ih onogf ope celnso ed sure levels. More than 2,500 validated canon coving 31 diffe con ype wre SASICES TLL) onnat cers covering 21 different cancer types were Edd he i eon EnUt e EA included in the analysis, making it one of the SL SEY WE TIE SITE i largest cohorts ever used to examine PFOA con Ou dig ince ha FOR Sra 5mpi, vg St tsMono and cancer. Our findings indicate that PFOA pone posioadth iy Peo En ER MRA exposure was positively associated with kidney SEI STII ee i Cha and testicular cancer in this Mid-Ohio Valley population. Because this s gel asurvivor Aone MESOI pwtdcec. doom population. Because this is largely a survivor `ccoohhoorrtt, rreesuulltss ffoor hhiigghhllyy ffaatal canncceerrsmmuussttbbee Fount I interpreted with caution. IL ll WET RReerfeenreenncceess. Is DE EE Tr DSR Armstrong BG. 1998. Effect of measurement error on epideISIC EESSE tee miological studies of environmental and occupational exposures. Occup Environ Med 55(10):651-656. 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