Case-Cohort StudyoftheAssociationbetweenPFASandSelectedCancersamong Participants intheAmericanCancerSociety's CancerPreventionStudyIILifeLink Cohort

BACKGROUND: Previous epidemiologicalstudiesfoundassociationsbetweenexposuretoper- andpolyfluoroalkyl substances(PFAS) andsomecancer types. Manystudiesconsideredhighlyexposedpopulations, sorelevancetoless-exposedpopulationscanbeuncertain. Additionally, manystudies considered onlycancersite, nothistology. OBJECTIVES: We conductedacase-cohort studywithintheAmericanCancerSociety's prospectiveCancerPreventionStudyII(CPS-II) LifeLink cohort toexamineassociationsbetweenPFASexposureandriskofselectedcancers, consideringhistologicsubtypes. METHODS: Serum specimenswerecollectedfromcohortparticipantsduringtheperiod1998-2001. Thisstudyincludedasubcohort(500men, 499 women) randomlyselectedfromparticipantswithoutpriorcancerdiagnosesatserumcollection, andallparticipantswithincident(afterserumcollection) first cancersofthebreast(femalesonly, n= 786), bladder(n= 401), kidney(n= 158), pancreas(n= 172), prostate(malesonly, n= 1,610) orhematologic system(n= 635). PFASconcentrations[perfluorooctanoic acid(PFOA), perfluorooctane sulfonate(PFOS), perfluorohexane sulfonicacid (PFHxS), andperfluorononanoic acid(PFNA)] weremeasuredinstoredserum. WeassessedassociationsbetweenPFASconcentrationsandincident cancers, bysiteandhistologicsubtype, usingmultivariableCoxproportionalhazardsmodelsstratified bysexandcontrollingforageandyearat blood draw, education, race/ethnicity, smoking, andalcoholuse. RESULTS: Serum PFOAconcentrationswerepositivelyassociatedwithrenalcellcarcinomaofthekidneyamongwomen[hazardratio(HR) and95% confidence interval(CI) perPFOAdoubling: 1.54(95% CI: 1.05,2.26)] butnotmen. Amongmen, weobservedapositiveassociationbetween PFHxS concentrationsandchroniclymphocyticleukemia/smalllymphocyticlymphoma[CLL/SLL, HRand95% CIperPFHxSdoubling: 1.34(95% CI: 1.02,1.75)]. Weobservedsomeheterogeneityofassociationsbyhistologicsubtypewithinsites. DISCUSSION: This studysupportsthepreviouslyobservedassociationbetweenPFOAandrenalcellcarcinomaamongwomenandsuggestsanassociation betweenPFHxSandCLL/SLLamongmen. ConsiderationofhistologicsubtypesmightbeimportantinfuturestudiesofPFAS-cancerassocia-