A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and cancer risk in humans

Figures & data

Table 1. Design of epidemiologic studies of perfluorooctanoic acid (PFOA) and cancer.

Reference	Study location	Study design	Study subjects	Comparison subjects	Follow-up	Exposure assessment	Outcome assessment	Adjustment factors	Comments
Ubel et al. 1980	Cottage Grove, Minnesota, United States	Cross-sectional and retrospective cohort mortality	Cross-sectional: ∼300 workers per year (∼90% of all workers) in health evaluations in 1976–1979 (∼50% of workers participating in all 3 years) Cohort: 3,688 workers employed for ≥ 6 months (of a total of 4,218 workers) at a facility that produced APFO	Cross-sectional: none Cohort: “A population group of the same demographic composition”	Cross-sectional: none; examinations in 1976–1979 Cohort: 1948 through 1978	Exposure classification based on employment only: all employees or all chemical plant employees at the facility	Cross-sectional: personal health examination Cohort: NR; death certificates obtained for 177 of 180 decedents	Cross-sectional: none Cohort: age and calendar period; stratified by sex	SMRs not reported
Gilliland and Mandel 1993	Cottage Grove, Minnesota, United States	Retrospective cohort mortality	2,788 male and 749 female workers (1,339 males and 245 females in the chemical division; 1,449 males and 504 females in the nonchemical division) employed for ≥ 6 months at a plant that produced PFOA	Minnesota white male population United States white female population	1947–1983 through 1989; mean = 25 years in chemical division, 26 years in nonchemical division	PFOA exposure classified based on job histories (exposed if employed for ≥ 1 month in chemical division); cumulative PFOA exposure estimated based on months employed in chemical division	Vital status ascertained for 100% of cohort from Social Security Administration, National Death Index, and additional tracing strategies; death certificates obtained for 99.5% of decedents from state health departments (family members for 2 deaths outside United States)	Age and calendar period for SIRs; stratified by sex Age at first employment, year of first employment, and duration of employment for RRs; stratified by sex where appropriate	–
Leonard et al. 2008	Parkersburg, West Virginia, United States	Retrospective cohort mortality	6,027 workers (81% male) ever employed at a polymer production plant, identified primarily through the DuPont Epidemiology Registry, which includes active and pensioned employees (N = 5,454), and through administrative records from the plant's human resources department (N = 573)	United States population, West Virginia population, and DuPont Region 1 worker population (72,882 workers in West Virginia, Ohio, Virginia, Kentucky, Indiana, Pennsylvania, Tennessee, and North Carolina, excluding Parkersburg site)	1948 through 2002; mean ± SD = 26 ± 15 years in males, 16 ± 10 years in females; interquartile range = 13–39 years in males, 9–22 years in females; range = < 1–55 years in males and females	Potential exposure to PFOA based on ever employment	Mortality surveillance through DuPont Epidemiology Registry, Social Security Administration, and National Death Index	Age, sex, and calendar period	–
Eriksen et al. 2009	Denmark	Prospective case-cohort	713 prostate cancer cases, 332 bladder cancer cases, 128 pancreatic cancer cases, and 67 liver cancer cases diagnosed after enrollment in a prospective cohort of 57,053 Danish-born adults aged 50–65 years with no prior cancer	680 men and 92 women without cancer randomly selected from the same prospective cohort	1993–1997 to 2006 Cancers diagnosed 0–12 years (median: 7 years) after cohort enrollment	Plasma PFOA and PFOS measured in samples taken at cohort entry Median (5th–95th percentile) PFOA, ng/mL Prostate cancer: 6.9 (3.4–14.1) Bladder cancer: 6.5 (2.7–13.4) Pancreatic cancer: 6.7 (3.0–12.8) Liver cancer: 5.4 (2.5–13.7) Noncancer men: 6.9 (3.2–13.3) Noncancer women: 5.4 (2.2–11.6)	Linkage to Danish Cancer Registry and Danish Pathology Data Bank	Age as time scale (all sites), education (prostate, bladder, liver), body mass index (prostate), dietary fat intake (prostate, pancreas), fruit and vegetable intake (prostate, pancreas), smoking status (bladder, pancreas, liver), smoking intensity (bladder, pancreas), smoking duration (bladder, pancreas), high-risk occupation (bladder, liver), alcohol intake (liver); hazards stratified by sex where appropriate	Spearman ρ = 0.70 for correlation between PFOA and PFOS
Lundin et al. 2009	Cottage Grove, Minnesota, United States	Retrospective cohort mortality	3,993 employees (80% male) employed for ≥ 1 year at an APFO manufacturing plant; 513 definitely exposed to APFO, 1,688 probably exposed, 1,792 nonexposed	Minnesota population	1947–1997 through 2002; mean = 31.3 years (29.3 years for definitely exposed, 31.6 years for probably exposed, 31.6 years for nonexposed)	Semi-quantitative job-exposure matrix with 3 exposure levels (definite, probable, or no/minimal) based on work history records and expert historical knowledge of the manufacturing process. Job-based exposure classification considered ever working in jobs at a given exposure level (definite, probable but not definite, or only nonexposed) or working ≥ 6 months in a job with definite exposure (high exposure), working 0–< 6 months in a job with definite exposure but ever working in a job with probable exposure (moderate exposure), or working only in nonexposed jobs (low exposure). Cumulative exposure classification used relative exposure weights (100, 30, 1; alternatives = 100, 50, 1 and 100, 10, 1) assigned to job-exposure matrix based on serum PFOA measurements from 131 employees in year 2000 (definite exposure = 2.6–5.2 ppm, probable exposure = 0.3–1.5 ppm), multiplied by sum of days of employment at each level	Vital records searches through National Death Index for nonactive employees not previously identified as deceased in earlier follow-up	Age, sex, and calendar period for SMRs Sex and year of birth for HRs (also considered age at cohort entry, smoking status, and wage type)	No change in results with 10-year lag or alternative weighting schemes
Vassiliadou et al. 2010	Athens and Argolida, Greece	Cross-sectional	40 cancer patients hospitalized at the Saint Savas Anticancer Hospital in Athens	56 healthy working employees at a research center undergoing their annual health check at the Medical Care Center of NCSR “Demokritos” in Athens (urban area) 86 ambulatory patients and healthy individuals undergoing a medical check at the General Hospital of Nafplio, Argolida (semi-urban/rural area)	None; blood samples collected in first half of 2009	PFOA and PFOS measured in serum	Cancer cases hospitalized with malignancy; noncancer controls undergoing routine medical examination	None	–
Bonefeld-Jorgensen et al. 2011	Nuuk, Greenland	Case-control	31 Greenland Inuit women with breast cancer (80% of all breast cancer cases in Greenland during sampling period) identified from Dronning Ingrids Hospital	115 (98 with data on PFOA and PFOS) Greenland Inuit women without breast cancer frequency-matched to cases on age and district, identified from two cross-sectional serological studies in randomly sampled women, with participation rates > 90% (Cote et al. 2006; Deutch et al. 2007)	None; enrollment period: 2000–2003	10 perfluorinated compounds including PFOA and PFOS measured in serum from cases at breast cancer diagnosis and from controls at study enrollment Serum PFOA (ng/mL) Cases: median: 2.5; 95% CI: 2.2, 3.4; range: 0.2–7.2 Controls: median: 1.6; 95% CI: 2.11, 2.9; range: 0.2–7.6	Cases identified from a single hospital where all breast cancer cases in Greenland are registered	Age, body mass index, full-term pregnancies, cotinine, breastfeeding, and menopausal status in adjusted models	Also measured polychlorinated biphenyl congeners, organochlorine compounds, lipids, and fatty acids in plasma; metals in whole blood; and cotinine, estradiol, and xenobiotic-induced transactivity of estrogen receptor, androgen receptor, and aryl hydrocarbon receptor in serum
Steenland and Woskie 2012	Parkersburg, West Virginia, United States	Retrospective cohort mortality	Same as Leonard et al. 2008, reduced to 5,791 workers with available date of birth and sufficiently detailed work history for estimation of PFOA serum levels over time	DuPont Appalachian region worker population (67,294 male and 19,404 female workers at plants in West Virginia, Ohio, Virginia, Kentucky, Indiana, Pennsylvania, Tennessee, and North Carolina, excluding Parkersburg site, from 1955–2009); also, United States population for 1940–2007 extrapolated to 2009	1948 through 2008; mean = 30 years	Time-varying job-exposure matrix based on 2,125 serum samples from 1,308 workers with measured PFOA concentrations taken in 1979–2004, used as a basis for regression models to estimate annual serum levels for each worker after grouping into 8 job category/job group combinations: 1) direct PFOA exposure in Teflon production area, including 2) chemical operators identified separately; 3) direct PFOA exposure in other copolymer production areas; 4) intermittent direct non-PFOA use jobs, including 5) tetrafluoroethylene monomer jobs identified separately; 6) maintenance jobs with intermittent direct or plant background PFOA exposures, including 7) Teflon/copolymer maintenance jobs identified separately; and 8) non-Teflon/copolymer production division jobs with no PFOA use. Mean estimated annual serum PFOA = 0.35 ppm (median: 0.23), mean cumulative exposure = 7.8 ppm-years (median: 4.3)	Mortality surveillance through National Death Index (1979–2008) and DuPont registry based on Social Security Administration and state death certificates	NR	Spearman ρ = 0.8 for correlation between modeled and measured serum PFOA at the job category/job group level (Woskie et al. 2012) “[T]etrafluoroethylene, used in the manufacture of a variety of fluoropolymers, has been identified as a rodent kidney carcinogen ... PFOA and tetrafluoroethylene are highly correlated potential exposures in this worker population.” (p.916) “Mesothelioma showed a significant positive exposure-response relation with PFOA in unlagged analyses, possibly driven by duration of employment, which is correlated with cumulative PFOA exposure.” (p.916)
Barry et al. 2013	Mid-Ohio Valley, Ohio and West Virginia, United States	Retrospective cohort	32,254 adults aged ≥ 20 years (of 54,457 adult participants; estimated participation rate = 81%) who lived, worked, or attended school for ≥ 1 year in one of six contaminated water districts near a chemical plant between 1950 and 3 December 2004, and/or were included in the cohort mortality study of plant workers, participated in at least one follow-up survey, and had estimates of PFOA exposure; includes 28,541 community workers never employed at the plant and 3,713 adults who worked at the plant for ≥ 1 day between 1948 and 2002	Internal referent	Age 20 years or age in 1952 (if older) through earliest of age at cancer, death, or last study survey (2008–2010 or 2010–2011); mean follow-up time = 32 years for community residents, 38 years for workers	Cumulative PFOA serum concentration estimated for each year of life from 1952 or birth (if later) through 2011 based on historical regional data including PFOA emission and dispersion patterns, personal residential history and water consumption, and a PFOA absorption, distribution, metabolism, and excretion model; also accounted for occupational exposure for plant workers (N = 3,713) using a job-exposure matrix based on job history and > 2,000 PFOA serum measurements taken over time from workers Median measured serum PFOA level in 2005–2006 = 24.2 ng/mL (range: 0.25–4,752) in community members, 112.7 ng/mL (range: 0.25–22,412) in 1,881 workers Median estimated annual serum PFOA level = 19.4 ng/mL (range: 2.8–9,217) in community members, 174.4 ng/mL (range: 5.2–3,683) in all workers	Self-report on mailed survey, followed by a request for medical records review of reported diagnoses or linkage to Ohio and West Virginia state cancer registries (1992 and 1993 onward, respectively) for confirmation; only validated cases (2,507 [70%] of 3,589 reported, with reviewable records obtained for 3,146 [88%]) included in analysis	Age (time scale), sex, education, time-varying smoking, and time-varying alcohol consumption; hazards stratified by 5-year birth period	Results were similar when using a 20-year lag or when based on all self-reported cancer cases (data not shown) Spearman ρ = 0.677 for correlation between model-predicted and observed serum PFOA levels in 43,449 community members in 2005–2006, although predicted median was lower than observed median (14.2 ppb vs. 24.3 ppb in original analysis; 13.7 ppb vs. NR in erratum) (Shin et al. 2011b)
Consonni et al. 2013	Gendorf, Germany; Dordrecht, the Netherlands; Spinetta Marengo, Italy; Thornton Cleveleys, United Kingdom; Bayonne, New Jersey, United States; and Parkersburg, West Virginia, United States	Retrospective cohort mortality	5,879 male workers (4,205 ever exposed to APFO) at all 6 tetrafluoroethylene (TFE) production sites in Europe and North America (excluding one small plant in North Carolina), including ever workers at 3 sites and workers employed for ≥ 6 months (West Virginia) or ≥ 1 year (Germany, Netherlands) at others	National populations	1950–2002 (TFE production period) through 2001–2008; mean = 25.3 years (total person-years = 148,843)	Job-exposure matrix with annual semiquantitative estimates of TFE and APFO exposure based on work history records and “sparse measurement data available from the plants”; also collected plant-level information on potential exposure (yes/no) to asbestos and vinyl chloride monomer	Vital status ascertained from population registries (Germany, the Netherlands, Italy), National Health Service (United Kingdom), or Social Security Administration (West Virginia and New Jersey), 98.8% complete; underlying causes of death obtained from death certificates and ICD codes provided by local, state, national, and company sources	Age and calendar period	Spearman ρ = 0.72 for correlation between TFE and APFO exposure estimates; no workers were exposed to APFO but not to TFE Results not shown for 778 women (683 at West Virginia site), including 16 deaths
Vieira et al. 2013	Mid-Ohio Valley, Ohio and West Virginia, United States (Athens, Meigs, Gallia, Washington, and Morgan Counties, Ohio; Wood, Mason, Wirt, Putnam, Jackson, Pleasants, Ritchie, and Cabell Counties, West Virginia)	Case-control	Incident cancer cases identified from Ohio Cancer Incidence Surveillance System (N = 7,869) and West Virginia Cancer Registry (N = 17,238), residing in the study area at diagnosis, with geocoding data, excluding cancer types with < 100 Ohio cases or not previously studied in animals or occupational cohorts, and cases diagnosed < 15 years of age	Controls for analysis of each of 18 cancer types = all other cancers excluding kidney, pancreatic, testicular, and liver cancers	None; cases diagnosed 1996 through 2005	Potential exposure to PFOA in drinking water estimated based on residence at diagnosis in one or any of 6 contaminated public water districts vs. noncontaminated water districts. 1995 median PFOA serum concentrations by public water district were previously estimated using a PFOA exposure model and > 45,000 serum measurements: Little Hocking, Ohio: 125 μg/L Lubeck, West Virginia: 65.8 μg/L Tupper Plains, Ohio: 23.9 μg/L Belpre, Ohio: 18.7 μg/L Pomeroy, Ohio: 10.7 μg/L Mason, West Virginia: 5.3 μg/L In Ohio only, based on street address, estimated annual serum PFOA level from 1951 to date of diagnosis (assuming residency at address for 10 years or lifetime in sensitivity analyses, with 0 or 10-year lag) using an existing PFOA exposure model incorporating environmental, exposure, and pharmacokinetic data (Shin et al. 2011a, 2011b). Categorized annual serum level at diagnosis or 10 years previously or cumulative serum level as very high, high, medium, low, or unexposed based on distribution among exposed	Incident cancers registered in Ohio and West Virginia cancer registries	Age, sex, diagnosis year, smoking status, insurance provider, and (in Ohio only) race	Results were comparable when using estimated cumulative PFOA serum exposure assuming 10-year latency and residency; annual PFOA serum exposure assuming 10-year residency and no latency; alternative control group including kidney, liver, pancreas, and testis cancer patients; or multiple imputation for missing smoking data (N = 2,452) and health insurance provider data (N = 1,824)
Yeung et al. 2013	Melbourne, Australia	Cross-sectional	66 diseased liver tissues (12 HCC [24 serum specimens]; 14 HCC with HCV [13 serum specimens]; 38 cirrhosis with HCV [38 serum specimens]; 2 amyloidosis or acute liver failure [4 serum specimens]) obtained from explanted livers at the time of liver transplantation at a single liver transplant unit	9 histologically normal control liver tissues obtained from patients resected for colorectal metastasis, with specimens taken well clear of the tumor margin; 25 serum specimens taken from healthy donors without known liver disease	None; case tissues and serum specimens obtained from 2004 through 2009, control tissues and serum specimens mostly obtained from 2007 through 2008	12 perfluoroalkyl and polyfluoroalkyl substances measured in liver and serum specimens	Liver disease cases identified from the liver tissue bank at the Victorian Liver Transplant Unit	None	Spearman ρ = −0.227 for correlation of PFOS in paired serum and liver tissue samples in HCC without HCV; 0.189 in HCC with HCV; 0.298 in HCV cirrhosis; P > 0.05 for all correlations Spearman ρ = 0.850 for correlation of PFOA and PFOS in control liver tissue; 0.708 in control serum
Hardell et al. 2014	Örebro, Sweden	Case-control	201 incident cases of prostate cancer with blood results, including 200 admitted for treatment at an oncology department at a single hospital in 2007–2011 + 2 previously untreated cases diagnosed during study period and identified from the control group – 1 without blood results; 79% participation rate	185 population controls without prior cancer individually matched to cases on age and county of residence, identified from Swedish population registry with one round of replacement; 60% participation rate, 54% after excluding those with prior cancer	None; enrollment period: 2007–2011	8 perfluorinated compounds including PFOA and PFOS measured in whole blood collected during same time period for cases and controls Whole blood PFOA (ng/mL) Cases: mean: 2.3; median: 2.0; range: 0.320–15 Controls: mean: 2.0; median: 1.9; range: 0.345–8.4	Consecutive, newly diagnosed patients with prostate cancer admitted for treatment with radiation or chemotherapy at the Department of Oncology at the University Hospital in Örebro	Age, body mass index, and year of blood sampling	“Somewhat higher” but statistically nonsignificant OR after using > 75th percentile as cutoff for PFOA (data not shown)
Innes et al. 2014	Mid-Ohio Valley, Ohio and West Virginia, United States	Cross-sectional	208 prevalent cases of colon and/or rectal cancer identified among adults aged ≥ 21 years who lived or worked for ≥ 1 year in one of six contaminated water districts near a chemical plant between 1950 and 3 December 2004, and participated in a baseline health survey, with complete data on all covariates of interest	47,151 adults without cancer from the same study group as the cases	None; survey period: 2005–2006	10 perfluorocarbon compounds including PFOA and PFOS measured in serum collected at the time of the health survey Median serum PFOA = 27.9 ng/mL (range: < 0.5–22.412) Mean ± SD serum PFOA = 86.6 ± 255.1 ng/mL “[S]erum levels of other [perfluoroalkyl acids] for which adequate data were available were comparable to general background levels in the U.S.”	Self-report of colon and/or rectal cancer diagnosis on mailed survey, followed by verification via medical chart review	Age, race, sex, years of education, annual household income, employment status/disability, marital status, smoking status, current alcohol consumption, vegetarian diet, regular exercise program, body mass index, menopausal status, comorbidity, metabolic/physiologic profile (serum lipid profiles, C-reactive protein, estradiol, and uric acid), and gastrointestinal symptoms (diarrhea, abdominal pain, nausea, bloating, blood stools, and indigestion) Further adjustment for other perfluoroalkyl acids, anemia, or diagnosed osteoarthritis, rheumatoid arthritis, and fibromyalgia or exclusion of those with low hemoglobin levels (N = 2,391, including 41 cases) did not alter the results	P-value for interaction = 0.04 for sex (inverse association for males), 0.09 for body mass index (inverse association for non-obese adults), 0.02 for year of diagnosis (inverse association for cases diagnosed in 2000 or later); no significant interaction by age or colorectal cancer treatment method Restricting the analysis of adults with serum PFOA ≤ 20 ng/mL (N = 19,201 subjects, including 84 cases) “substantially strengthened the linear, inverse relationship of PFOA to [colorectal cancer] diagnosis”; age-adjusted OR for highest vs. lowest quartile = 0.4 (95% CI: 0.2, 0.7; P-trend = 0.009) Results were unchanged after excluding primary rectal cancer cases (N = 29), cases undergoing current treatment (N = 21), or those who had received chemotherapy (N = 109), or including unconfirmed self-reported colorectal cancer cases (N = 73)

Abbreviations: APFO: ammonium perfluorooctanoate; CI: confidence interval; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HR: hazard ratio; ICD: International Classification of Diseases; NR: not reported; OR: odds ratio; PFOA (C8): perfluorooctanoic acid; PFOS: perfluorooctanesulfonate; RR: rate ratio or relative risk; SD: standard deviation; SIR: standardized incidence ratio; SMR: standardized mortality ratio; TFE: tetrafluoroethylene.

Table 2. Results of epidemiologic studies of perfluorooctanoic acid (PFOA) and cancer

	Ubel et al. 1980				Gilliland and Mandel 1993				Leonard et al. 2008					Eriksen et al. 2009				Lundin et al. 2009				Vassiliadou et al. 2010				Bonefeld-Jorgensen et al. 2011
Organ site	Exposure category	No. deaths	Relative risk	95% CI	Exposure category	No. deaths	Relative risk	95% CI	Exposure category	No. deaths	Relative risk	95% CI	Organ site	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. deaths	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI
All sites	All workers	NR (180 total deaths; 159 males, 21 females)	Cross-sectional: “No health problems related to exposure to fluorochemicals were encountered among those examined.” Cohort: “The number of deaths among females was too few to permit statistical evaluation. Results of mortality analyses for the males indicated no disagreement between the observed mortality and that expected. This was true of all the various causes of death and also of various specific causes of death due to cancer. In addition, mortality analyses for the chemical workers at the plant revealed no disagreements between observed and expected mortality for any cause of death.” (p.588)	NR	Female workers Male workers Male chemical workers Per year of first employment Per year of age at first employment Per year of duration of employment Per month of employment in chemical division [HRs for males only]	17 103 40 103 males	SMR = 0.71 SMR = 1.05 SMR = 1.10 HR = 0.97 HR = 1.08 HR = 0.97 HR = 1.00	0.42, 1.14 0.86, 1.27 0.79, 1.50 P = 0.11 P = 0.0001 P = 0.002 P = 0.2	Workers vs. US Males Females Workers vs. West Virginia Males Females Workers vs. DuPont Region 1 Males Females	234 total 222 males 12 females	SMR = 0.74 SMR = 0.74 SMR = 0.87 SMR = 0.69 SMR = 0.68 SMR = 0.79 SMR = 1.02 SMR = 1.00 SMR = 1.49	0.65, 0.84 0.64, 0.84 0.45, 1.51 0.60, 0.78 0.60, 0.78 0.41, 1.39 0.89, 1.16 0.88, 1.14 0.77, 2.60	All sites	–	–	–	–	Never Probable/never definite Ever definite	108 119 19	SMR = 0.78 SMR = 0.94 SMR = 0.87	0.64, 0.95 0.78, 1.12 0.52, 1.35	PFOA in serum (ng/mL): - Mean, male cases - Mean, female cases - Median, male cases - Median, female cases - Range, male cases - Range, female cases - Mean, Athens males - Mean, Athens females - Median, Athens males - Median, Athens females - Range, Athens males - Range, Athens females - Mean, Argolida males - Mean, Argolida females - Median, Argolida males - Median, Argolida females - Range, Argolida males - Range, Argolida females	Cases: 17 males, 23 females Athens controls: 27 males, 29 females Argolida controls: 27 males, 59 females	[No RRs] 2.79 1.95 2.27 1.85 1.29–6.89 0.75–3.26 3.88 2.08 3.14 1.70 1.68–10.21 0.57–6.57 2.05 1.92 1.81 1.71 0.48–5.60 0.55–6.29	Analysis of variance P < 0.05	–	–	–	–
Buccal cavity and pharynx	–	–		–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	4	SMR = 0.52 SMR = 0.61 SMR = 1.17	0.14, 1.33 0.17, 1.56 0.32, 3.00	Buccal cavity and pharynx	–	–	–	–	Never Probable/never definite Ever definite	1 1 0	SMR = 0.39 SMR = 0.40 SMR = NR	0.01, 2.14 0.01, 2.25 0.00, 7.78	–	–	–	–	–	–	–	–
Digestive system/gastrointestinal	–	–	–	–	Female workers Male workers Male chemical workers	2 24 9	SMR = 0.44 SMR = 0.90 SMR = 0.92	0.05, 1.59 0.57, 1.33 0.42, 1.75	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	51	SMR = 0.67 SMR = 0.72 SMR = 0.94	0.50, 0.88 0.54, 0.95 0.70, 1.24	Digestive system/gastrointestinal	–	–	–	–	Never Probable/never definite Ever definite	30 27 4	SMR = 0.90 SMR = 0.87 SMR = 0.75	0.61, 1.28 0.57, 1.26 0.20, 1.91	–	–	–	–	–	–	–	–
Esophagus	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	4	SMR = 0.41 SMR = 0.47 SMR = 0.83	0.11, 1.05 0.13, 1.20 0.23, 2.13	Esophagus	–	–	–	–	Never Probable/never definite Ever definite	2 1 1	SMR = 0.59 SMR = 0.31 SMR = 1.54	0.07, 2.13 0.01, 1.70 0.04, 8.57	–	–	–	–	–	–	–	–
Stomach	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 0.30 SMR = 0.36 SMR = 0.52	0.06, 0.88 0.07, 1.05 0.11, 1.52	Stomach	–	–	–	–	Never Probable/never definite Ever definite	3 4 0	SMR = 0.74 SMR = 1.06 SMR = NR	0.15, 2.15 0.29, 2.71 0.00, 5.82	–	–	–	–	–	–	–	–
Colorectum	–	–	–	–	–	–	–	–	–	–	–	–	Colorectum	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Colon	–	–	–	–	Male workers Male chemical workers	9 4	SMR = 0.96 SMR = 1.15	0.44, 1.81 0.31, 4.01	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	17	SMR = 0.67 SMR = 0.68 SMR = 0.78	0.39, 1.07 0.40, 1.09 0.46, 1.25	Colon	–	–	–	–	Never Probable/never definite Ever definite	16 10 2	SMR = 1.30 SMR = 0.88 SMR = 1.07	0.75, 2.12 0.42, 1.62 0.13, 3.86	–	–	–	–	–	–	–	–
Rectum	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	5	SMR = 0.92 SMR = 0.84 SMR = 1.32	0.30, 2.14 0.27, 1.95 0.43, 3.08	Rectum	–	–	–	–	Never Probable/never definite Ever definite	1 3 0	SMR = 0.40 SMR = 1.28 SMR = NR	0.01, 2.22 0.26, 3.76 0.00, 9.24	–	–	–	–	–	–	–	–
Liver (with or without bile ducts)	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	8	SMR = 0.99 SMR = 1.15 SMR = 1.45	0.43, 1.96 0.50, 2.27 0.63, 2.86	Liver (with or without bile ducts)	PFOA quartile 1 PFOA quartile 2 PFOA quartile 3 PFOA quartile 4 Per 1 ng/mL plasma PFOA	17 17 17 16 67	RR = 1.00 RR = 1.00 RR = 0.49 RR = 0.60 RR = 0.95	Referent 0.44, 2.23 0.22, 1.09 0.26, 1.37 0.86, 1.06	Never Probable/never definite Ever definite	1 2 0	SMR = 0.33 SMR = 0.71 SMR = NR	0.01, 1.83 0.09, 2.55 0.00, 7.60	–	–	–	–	–	–	–	–
Pancreas	–	–	–	–	Male workers Male chemical workers	8 4	SMR = 1.43 SMR = 1.96	0.62, 2.83 0.53, 5.01	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	11	SMR = 0.71 SMR = 0.80 SMR = 0.98	0.36, 1.28 0.40, 1.43 0.49, 1.76	Pancreas	PFOA quartile 1 PFOA quartile 2 PFOA quartile 3 PFOA quartile 4 Per 1 ng/mL plasma PFOA	32 32 32 32 128	RR = 1.00 RR = 0.88 RR = 1.33 RR = 1.55 RR = 1.03	Referent 0.49, 1.57 0.74, 2.38 0.85, 2.80 0.98, 1.10	Never Probable/never definite Ever definite Low Moderate Moderate or high High < 1 year 1–4.9 years ≥ 1 year ≥ 5 years	5 7 1 5 8 8 0 7 4 6 2	SMR = 0.70 SMR = 1.04 SMR = 0.85 HR = 1.0 HR = 1.7 HR = 1.6 HR = NR HR = 1.0 HR = 2.3 HR = 1.8 HR = 1.3	0.23, 1.63 0.42, 2.14 0.02, 4.74 Referent 0.5, 5.2 0.5, 4.8 NR Referent 0.7, 8.1 0.6, 5.6 0.3, 6.4	–	–	–	–	–	–	–	–
Other digestive	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 1.30 SMR = 1.26 SMR = 2.27	0.27, 3.79 0.26, 3.67 0.47, 6.62	Other digestive	–	–	–	–	Never Probable/never definite Ever definite	2 0 0	SMR = 2.11 SMR = NR SMR = NR	0.25, 7.60 0.04, 4.15 0.00, 24.2	–	–	–	–	–	–	–	–
Respiratory	–	–	–	–	Female workers Male workers Male chemical workers	4 31 12	SMR = 0.95 SMR = 1.02 SMR = 1.07	0.26, 2.43 0.69, 1.45 0.55, 1.86	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	72	SMR = 0.63 SMR = 0.52 SMR = 0.86	0.50, 0.80 0.40, 0.65 0.67, 1.08	Respiratory	–	–	–	–	Never Probable/never definite Ever definite	32 38 9	SMR = 0.78 SMR = 0.99 SMR = 1.27	0.53, 1.10 0.70, 1.36 0.58, 2.40	–	–	–	–	–	–	–	–
Larynx	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 0.76 SMR = 0.66 SMR = 1.95	0.16, 2.21 0.14, 1.94 0.40, 5.69	Larynx	–	–	–	–	Never Probable/never definite Ever definite	1 1 1	SMR = 0.86 SMR = 0.91 SMR = 4.72	0.02, 4.79 0.02, 5.03 0.12, 26.23	–	–	–	–	–	–	–	–
Lung	–	–	–	–	Male workers Male chemical workers	29 11	SMR = 1.00 SMR = 1.03	0.67, 1.44 0.51, 1.84	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	66	SMR = 0.61 SMR = 0.49 SMR = 0.82	0.47, 0.77 0.38, 0.63 0.64, 1.05	Lung	–	–	–	–	Never Probable/never definite Ever definite	30 37 8	SMR = 0.76 SMR = 1.00 SMR = 1.17	0.51, 1.09 0.71, 1.38 0.51, 2.31	–	–	–	–	–	–	–	–
Other respiratory	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 2.85 SMR = 3.10 SMR = 1.51	0.59, 8.31 0.64, 9.06 0.31, 4.41	Other respiratory	–	–	–	–	Never Probable/never definite Ever definite	1 0 0	SMR = 2.30 SMR = NR SMR = NR	0.03, 12.76 0.00, 9.05 0.00, 45.63	–	–	–	–	–	–	–	–
Mesothelioma	–	–	–	–	–	–	–	–	–	–	–	–	Mesothelioma	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Breast	–	–	–	–	Female workers	3	SMR = 0.51	0.10, 1.49	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	2	SMR = 0.55 SMR = 0.57 SMR = 0.70	0.07, 1.97 0.07, 2.05 0.09, 2.54	Breast	–	–	–	–	Never Probable/never definite Ever definite	4 2 0	SMR = 0.64 SMR = 0.42 SMR = NR	0.17, 1.63 0.05, 1.53 0.00, 12.54	–	–	–	–	Per ng/mL of serum PFOA	31 cases and 98 controls with PFOA 7 cases and 69 controls with PFOA and covariates	OR = 1.07 (unadjusted, all subjects) OR = 0.94 (unadjusted, subjects with covariate data) OR = 1.20 (adjusted)	0.88, 1.31 (unadjusted, all subjects) 0.05, 1.38 (unadjusted, subjects with covariate data) 0.77, 1.88 (adjusted)
Genitourinary	–	–	–	–	–	–	–	–	–	–	–	–	Genitourinary	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Female genital	–	–	–	–	Female workers	2	SMR = 0.59	0.07, 2.14	–	–	–	–	Female genital	–	–	–	–	Never Probable/never definite Ever definite	1 4 0	SMR = 0.27 SMR = 1.38 SMR = NR	0.01, 1.50 0.38, 3.54 0.00, 25.35	–	–	–	–	–	–	–	–
Ovary	–	–	–	–	–	–	–	–	–	–	–	–	Ovary	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Uterus	–	–	–	–	–	–	–	–	–	–	–	–	Uterus	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Cervix	–	–	–	–	–	–	–	–	–	–	–	–	Cervix	–	–	–	–	Never Probable/never definite Ever definite	1 1 0	SMR = 1.96 SMR = 2.68 SMR = NR	0.05, 10.92 0.07, 14.89 0.00, 168.7	–	–	–	–	–	–	–	–
Other female genital	–	–	–	–	–	–	–	–	–	–	–	–	Other female genital	–	–	–	–	Never Probable/never definite Ever definite	0 3 0	SMR = NR SMR = 1.89 SMR = NR	0.00, 1.81 0.39, 5.52 0.00, 46.40	–	–	–	–	–	–	–	–
Male genital	–	–	–	–	–	–	–	–	–	–	–	–	Male genital	–	–	–	–	Never Probable/never definite Ever definite	4 10 3	SMR = 0.35 SMR = 0.99 SMR = 1.93	0.09, 0.89 0.47, 1.82 0.40, 5.65	–	–	–	–	–	–	–	–
Prostate	–	–	–	–	Male workers Male chemical workers Male chemical workers for > 15 y Per year of first employment Per year of age at first employment Per year of duration of employment Per month of employment in chemical division Per year of employment in chemical division Per 10 years of employment in chemical division	6 4 NR 6	SMR = 0.99 SMR = 2.03 SMR = 1.61 HR = 1.01 HR = 1.09 HR = 0.93 HR = 1.01 HR = 1.13 HR = 3.3	0.36, 2.15 0.55, 4.59 0.32, 4.70 P = 0.9 P = 0.06 P = 0.18 P = 0.03 1.01, 1.27 1.02, 10.6	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	12	SMR = 0.52 SMR = 0.58 SMR = 0.65	0.27, 0.91 0.30, 1.00 0.34, 1.14	Prostate	PFOA quartile 1 PFOA quartile 2 PFOA quartile 3 PFOA quartile 4 Per 1 ng/mL plasma PFOA	179 178 178 178 713	RR = 1.00 RR = 1.09 RR = 0.94 RR = 1.18 RR = 1.03	Referent 0.78, 1.53 0.67, 1.32 0.84, 1.65 0.99, 1.07	Never Probable/never definite Ever definite Low Moderate Moderate or high High < 1 year 1–4.9 years ≥ 1 year ≥ 5 years	4 9 3 4 10 12 2 8 1 8 7	SMR = 0.36 SMR = 0.93 SMR = 2.10 HR = 1.0 HR = 3.0 HR = 3.2 HR = 6.6 HR = 1.0 HR = 0.4 HR = 2.0 HR = 3.7	0.10, 0.92 0.42, 1.76 0.43, 6.13 Referent 0.9, 9.7 1.0, 10.3 1.1, 37.7 Referent 0.1, 3.6 1.3, 10.4 0.7, 5.3	–	–	–	–	–	–	–	–
Testis (with or without other male genital)	–	–	–	–	Male workers Male chemical workers	1 1	SMR = 1.09 SMR = 2.28	0.01, 6.05 0.03, 12.66	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	1	SMR = 0.87 SMR = 0.76 SMR = 1.70	0.02, 4.84 0.02, 4.22 0.04, 9.46	Testis (with or without other male genital)	–	–	–	–	Never Probable/never definite Ever definite	0 0 0	–	–	–	–	–	–	–	–	–	–
Other male genital	–	–	–	–	–	–	–	–	–	–	–	–	Other male genital	–	–	–	–	Never Probable/never definite Ever definite	0 1 0	SMR = NR SMR = 2.33 SMR = NR	0.00, 8.96 0.06, 12.96 0.00, 30.13	–	–	–	–	–	–	–	–
Urinary	–	–	–	–	–	–	–	–	–	–	–	–	Urinary	–	–	–	–	Never Probable/never definite Ever definite	6 5 0	SMR = 0.89 SMR = 0.79 SMR = NR	0.32, 1.93 0.26, 1.85 0.00, 3.25	–	–	–	–	–	–	–	–
Kidney (with or without other urinary)	–	–	–	–	–	–	–	–	Workers vs. US Males Workers vs. West Virginia Males Workers vs. DuPont Region 1 Males	12 (all male)	SMR = 1.52 SMR = 1.56 SMR = 1.51 SMR = 1.55 SMR = 1.81 SMR = 1.85	0.78, 2.65 0.80, 2.72 0.78, 2.64 0.80, 2.72 0.94, 3.16 0.95, 3.23	Kidney (with or without other urinary)	–	–	–	–	Never Probable/never definite Ever definite	2 2 0	SMR = 0.50 SMR = 0.53 SMR = NR	0.06, 1.81 0.06, 1.90 0.00, 4.92	–	–	–	–	–	–	–	–
Bladder (with or without other urinary)	–	–	–	–	Male workers Male chemical workers	3 1	SMR = 1.37 SMR = 1.33	0.28, 4.01 0.02, 7.40	Workers vs. US Males Workers vs. West Virginia Males Workers vs. DuPont Region 1 Males	7 (all male)	SMR = 1.00 SMR = 1.01 SMR = 1.03 SMR = 1.05 SMR = 1.30 SMR = 1.31	0.40, 2.06 0.41, 2.09 0.41, 2.12 0.42, 2.16 0.52, 2.69 0.53, 2.69	Bladder (with or without other urinary)	PFOA quartile 1 PFOA quartile 2 PFOA quartile 3 PFOA quartile 4 Per 1 ng/mL plasma PFOA	84 82 83 83 332	RR = 1.00 RR = 0.71 RR = 0.92 RR = 0.81 RR = 1.00	Referent 0.46, 1.07 0.61, 1.39 0.53, 1.24 0.95, 1.05	Never Probable/never definite Ever definite Low Moderate Moderate or high High < 1 year 1–4.9 years ≥ 1 year ≥ 5 years	4 3 0 4 3 3 0 4 2 3 1	SMR = 1.44 SMR = 1.20 SMR = NR HR = 1.0 HR = 0.8 HR = 0.7 HR = NR HR = 1.0 HR = 2.2 HR = 1.7 HR = 1.2	0.39, 3.67 0.25, 3.50 0.0, 9.57 Referent 0.2, 3.6 0.2, 3.4 NR Referent 0.4, 8.1 0.4, 7.8 0.1, 10.7	–	–	–	–	–	–	–	–
Malignant melanoma	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 0.56 SMR = 0.52 SMR = 0.68	0.12, 1.63 0.11, 1.51 0.14, 1.97	Malignant melanoma	–	–	–	–	Never Probable/never definite Ever definite	2 2 0	SMR = 1.05 SMR = 1.09 SMR = NR	0.13, 3.79 0.13, 3.95 0.00, 8.37	–	–	–	–	–	–	–	–
Soft tissue	–	–	–	–	–	–	–	–	–	–	–	–	Soft tissue	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Brain/central nervous system	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	9	SMR = 1.00 SMR = 1.06 SMR = 1.27	0.46, 1.90 0.48, 2.01 0.58, 2.40	Brain/central nervous system	–	–	–	–	Never Probable/never definite Ever definite	2 5 0	SMR = 0.44 SMR = 1.16 SMR = NR	0.05, 1.59 0.37, 2.70 0.00, 3.81	–	–	–	–	–	–	–	–
Thyroid (with or without other endocrine)	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	3	SMR = 3.12 SMR = 2.86 SMR = 6.29	0.64, 9.12 0.59, 8.35 1.30, 18.37	Thyroid (with or without other endocrine)	–	–	–	–	Never Probable/never definite Ever definite	1 0 0	SMR = 2.16 SMR = NR SMR = NR	0.05, 12.00 0.00, 8.45 0.00, 42.96	–	–	–	–	–	–	–	–
Bone	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	2	SMR = 2.39 SMR = 2.19 SMR = 6.48	0.29, 8.64 0.27, 7.90 0.78, 23.42	Bone	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Lymphatic and hematopoietic	–	–	–	–	Female workers Male workers Male chemical workers	3 13 5	SMR = 1.47 SMR = 1.09 SMR = 1.05	0.30, 4.29 0.57, 1.84 0.34, 2.45	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	32	SMR = 1.04 SMR = 1.02 SMR = 1.29	0.71, 1.47 0.69, 1.43 0.88, 1.82	Lymphatic and hema- topoietic	–	–	–	–	Never Probable/never definite Ever definite	14 14 1	SMR = 0.90 SMR = 0.96 SMR = 0.37	0.49, 1.51 0.53, 1.61 0.01, 2.08	–	–	–	–	–	–	–	–
Non-Hodgkin lymphoma (with or without Hodgkin lymphoma)	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	9	SMR = 0.77 SMR = 0.78 SMR = 1.08	0.35, 1.46 0.35, 1.47 0.50, 2.05	Non-Hodgkin lymphoma (with or without Hodgkin lymphoma)	–	–	–	–	Never Probable/never definite Ever definite	1 2 0	SMR = 0.84 SMR = 1.80 SMR = NR	0.02, 4.65 0.22, 6.51 0.00, 19.45	–	–	–	–	–	–	–	–
Hodgkin lymphoma	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	2	SMR = 0.98 SMR = 1.01 SMR = 1.55	0.12, 3.56 0.12, 3.67 0.19, 5.60	Hodgkin lymphoma	–	–	–	–	Never Probable/never definite Ever definite	1 0 0	SMR = 1.09 SMR = NR SMR = NR	0.03, 6.04 0.00, 4.21 0.00, 18.69	–	–	–	–	–	–	–	–
Multiple myeloma	–	–	–	–	–	–	–	–	–	–	–	–	Multiple myeloma	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Leukemia (with or without aleukemia)	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	13	SMR = 1.12 SMR = 1.04 SMR = 1.22	0.60, 1.91 0.55, 1.78 0.65, 2.08	Leukemia (with or without aleukemia)	–	–	–	–	Never Probable/never definite Ever definite	4 7 1	SMR = 0.68 SMR = 1.27 SMR = 0.96	0.18, 1.73 0.51, 2.61 0.02, 5.34	–	–	–	–	–	–	–	–
Other lymphopoietic	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	8	SMR = 1.47 SMR = 1.47 SMR = 1.78	0.63, 2.89 0.64, 2.90 0.77, 3.50	Other lymphopoietic	–	–	–	–	Never Probable/never definite Ever definite	8 5 0	SMR = 1.07 SMR = 0.71 SMR = NR	0.46, 2.01 0.23, 1.66 0.00, 2.96	–	–	–	–	–	–	–	–
Other malignant neoplasms	–	–	–	–	–	–	–	–	Workers vs. US Workers vs. West Virginia Workers vs. DuPont Region 1	24	SMR = 0.94 SMR = 0.74 SMR = 1.52	0.60, 1.40 0.47, 1.10 0.97, 2.26	Other malignant neoplasms	–	–	–	–	Never Probable/never definite Ever definite	11 11 2	SMR = 1.14 SMR = 1.22 SMR = 1.23	0.57, 2.04 0.61, 2.18 0.15, 4.45	–	–	–	–	–	–	–	–

	Steenland and Woskie 2012				Barry et al. 2013				Consonni et al. 2013				Vieira et al. 2013				Yeung et al. 2013				Hardell et al. 2014				Innes et al. 2014
Organ site	Exposure category	No. deaths	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. deaths	Relative risk	95% CI	Organ site	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI
Leukemia (with or without aleukemia)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US With 10-yr lag: 0–< 798 ppm-yrs 798–< 1,379 ppm-yrs 1,379–< 2,384 ppm-yrs ≥ 2,384 ppm-yrs	62 68 83 91 304 304 69 69 76 79	SMR = 0.93 SMR = 0.90 SMR = 0.95 SMR = 0.94 SMR = 0.93 SMR = 0.74 SMR = 0.97 SMR = 0.91 SMR = 0.95 SMR = 0.92	0.72, 1.20 0.70, 1.14 0.75, 1.76 0.76, 1.16 0.83, 1.04 0.66, 0.83 0.75, 1.22 0.71, 1.15 0.75, 1.19 0.73, 1.15	–	–	–	–	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	28 (11 low TFE) 51 (42 low TFE) 53 (3 low TFE) 55 (0 low TFE) 159	SMR = 0.70 (0.72 low TFE) SMR = 0.78 (0.78 low TFE) SMR = 0.81 (0.50 low TFE) SMR = 0.78 (0.00 low TFE) P-trend = 0.70 SMR = 0.79	0.46, 1.01 (0.36, 1.30 low TFE) 0.58, 1.02 (0.56, 1.05 low TFE) 0.61, 1.06 (0.10, 1.46 low TFE) 0.59, 1.02 (NR low TFE) 0.67, 0.92	All sites	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Buccal cavity and pharynx	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	18 17 community 1 worker	HR = 0.89 (no lag) HR = 0.66 (10-yr lag)	0.65, 1.22 (no lag) 0.43, 1.02 (10-yr lag)	–	–	–	–	Buccal cavity and pharynx	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Digestive system/gastrointestinal	–	–	–	–	–	–	–	–	Ever exposed to APFO	50	SMR = 0.91	0.68, 1.20	Digestive system/gastrointestinal	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Esophagus	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	15 12 community 3 workers	HR = 0.96 (no lag) HR = 0.97 (10-yr lag)	0.70, 1.32 (no lag) 0.72, 1.31 (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	0 (0 low TFE) 4 (4 low TFE) 4 (1 low TFE) 3 (0 low TFE) 11	SMR = 0.00 (0.00 low TFE) SMR = 1.62 (1.92 low TFE) SMR = 1.54 (3.89 low TFE) SMR = 1.16 (0.00 low TFE) P-trend = 0.60 SMR = 1.44	NR (NR low TFE) 0.44, 4.14 (0.52, 4.92 low TFE) 0.42, 3.93 (0.10, 21.66 low TFE) 0.24, 3.39 (NR low TFE) 0.72, 2.57	Esophagus	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Stomach	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	12 11 community 1 worker	HR = 0.72 (no lag) HR = 0.77 (10-yr lag)	0.45, 1.14 (no lag) 0.49, 1.22 (10-yr lag)	Ever exposed to APFO	5	SMR = 0.52	0.17, 1.21	Stomach	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Colorectum	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	264 223 community 41 workers	HR = 0.99 (no lag) HR = 0.99 (10-yr lag)	0.92, 1.07 (no lag) 0.92, 1.07 (10-yr lag)	–	–	–	–	Colorectum	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	383 180 18 55 66 44 20 72 64 63 13	OR = 0.9 OR = 0.9 OR = 1.2 OR = 0.9 OR = 1.2 OR = 0.7 OR = 0.7 OR = 1.0 OR = 0.9 OR = 1.3 OR = 0.6	0.8, 1.0 0.8, 1.1 0.7, 2.1 0.7, 1.2 0.9, 1.6 0.5, 1.0 0.5, 1.2 0.8, 1.3 0.7, 1.2 1.0, 1.7 0.3, 1.0	–	–	–	–	–	–	–	–	Quartile 1 (0.25– 13.4 ng/mL PFOA) Quartile 2 (13.5– 27.8 ng/mL PFOA) Quartile 3 (27.9–71.2 ng/mL PFOA) Quartile 4 (≥ 71.3 ng/mL PFOA) Per ng/mL PFOA Residents since ≤ 1995, cases diagnosed ≥ 2000 Quartile 1 Quartile 2 Quartile 3 Quartile 4	58 36 49 65 28 7 21 15	OR = 1.00 OR = 0.48 OR = 0.51 OR = 0.64 P-trend = 0.002 OR = 1.00 OR = 1.00 OR = 0.25 OR = 0.37 OR = 0.43 P-trend = 0.001	Referent 0.31, 0.75 0.34, 0.77 0.44, 0.94 1.00, 1.00 Referent 0.11, 0.55 0.19, 0.70 0.24, 0.78
Colon	–	–	–	–	–	–	–	–	Ever exposed to APFO	7	SMR = 0.48	0.19, 0.99	Colon	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Rectum	–	–	–	–	–	–	–	–	Ever exposed to APFO	6	SMR = 1.03	0.38, 2.25	Rectum	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Liver (with or without bile ducts)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	4 0 5 1 10 10	SMR = 2.39 SMR = 0.00 SMR = 2.01 SMR = 0.32 SMR = 1.07 SMR = 0.77	0.65, 6.13 0.00, 1.81 0.65, 4.68 0.01, 1.76 0.51, 1.96 0.35, 1.47	Per unit of logged cumulative serum PFOA (ng/mL)	9 8 community 1 worker	HR = 0.73 (no lag) HR = 0.74 (10-yr lag)	0.43, 1.23 (no lag) 0.43, 1.26 (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	1 (0 low TFE) 1 (1 low TFE) 2 (0 low TFE) 4 (0 low TFE) 7	SMR = 0.72 (0.00 low TFE) SMR = 0.70 (0.85 low TFE) SMR = 1.25 (0.00 low TFE) SMR = 2.14 (0.00 low TFE) P-trend = 0.24 SMR = 1.43	0.02, 4.02 (NR low TFE) 0.02, 3.87 (0.02, 4.71 low TFE) 0.15, 4.52 (NR low TFE) 0.58, 5.49 (NR low TFE) 0.57, 2.94	Liver (with or without bile ducts)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	23 11 1 3 3 4 1 4 4 3 0	OR = 1.1 OR = 1.0 OR = 1.4 OR = 1.0 OR = 1.0 OR = 1.3 OR = 0.8 OR = 1.1 OR = 0.9 OR = 1.0 OR = NR	0.7, 1.6 0.5, 1.9 0.2, 10.5 0.3, 3.1 0.3, 3.3 0.5, 3.5 0.1, 5.6 0.4, 3.1 0.3, 2.5 0.3, 3.1 NR	PFOA in serum (ng/mL): - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC PFOA in liver (ng/g) - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC Ratio of PFOA in liver vs. paired serum - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC	HCC without HCV: 24 serum, 12 liver tissue, 11 paired HCC with HCV: 13 serum, 14 liver tissue, 12 paired	[No RRs] 2.82 ± 1.52 2.48 1.03–6.96 4.17 ± 2.50 3.43 0.706–11.0 0.589 ± 0.471 0.495 0.103–1.82 0.516 ± 0.409 0.454 0.101–1.61 0.28 ± 0.30 0.14 0.04–1.03 0.15 ± 0.11 0.13 0.02–0.39	Kruskal-Wallis rank test for group difference in liver-to-serum ratio: P > 0.05	–	–	–	–	–	–	–	–
													Liver, continued	–	–	–	–	PFOA in serum (ng/mL): - Mean ± SD, HCV - Median, HCV - Range, HCV - Mean ± SD, normal - Median, normal - Range, normal PFOA in liver (ng/g) - Mean ± SD, HCV - Median, HCV - Range, HCV - Mean ± SD, normal - Median, normal - Range, normal Ratio of PFOA in liver vs. paired serum - Mean ± SD, HCV - Median, HCV - Range, HCV	HCV cirrhosis: 38 serum, 38 liver tissue, 32 paired Normal: 25 serum, 9 liver tissue, 0 paired	[No RRs] 5.25 ± 6.91 3.55 0.700–45.5 2.38 ± 1.21 2.34 0.437–5.90 0.518 ± 0.474 0.416 0.160–2.25 0.620 ± 0.325 0.506 0.335–1.22 0.16 ± 0.15 0.10 0.01–0.74	Kruskal-Wallis rank test for group difference in liver-to-serum ratio: P > 0.05	–	–	–	–	–	–	–	–
Pancreas	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	4 4 5 5 18 18	SMR = 1.18 SMR = 1.02 SMR = 1.09 SMR = 0.92 SMR = 1.04 SMR = 0.85	0.32, 3.03 0.28, 2.61 0.35, 2.54 0.30, 2.16 0.62, 1.64 0.51, 1.35	Per unit of logged cumulative serum PFOA (ng/mL)	24 21 community 3 workers	HR = 1.00 (no lag) HR = 0.96 (10-yr lag)	0.78, 1.29 (no lag) 0.75, 1.22 (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	10 3 (1 low TFE) 0 (0 low TFE) 4 (0 low TFE) 6 (0 low TFE)	SMR = 1.66 (1.48 low TFE) SMR = 0.00 (0.00 low TFE) SMR = 1.30 (0.00 low TFE) SMR = 1.84 (0.00 low TFE) P-trend = 0.34 SMR = 1.05	0.34, 4.84 (0.04, 8.26 low TFE) NR (NR low TFE) 0.35, 3.33 (NR low TFE) 0.67, 4.00 (NR low TFE) 0.51, 1.94	Pancreas	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	58 25 2 8 10 9 4 12 10 9 2	OR = 1.0 OR = 0.9 OR = 1.0 OR = 0.9 OR = 1.3 OR = 1.1 OR = 1.1 OR = 1.3 OR = 0.9 OR = 1.1 OR = 0.6	0.8, 1.3 0.6, 1.4 0.2, 4.1 0.4, 1.8 0.7, 2.5 0.6, 2.1 0.4, 3.0 0.7, 2.3 0.5, 1.7 0.6, 2.3 0.1, 2.5	–	–	–	–	–	–	–	–	–	–	–	–
Other digestive	–	–	–	–	–	–	–	–	–	–	–	–	Other digestive	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Respiratory	–	–	–	–	–	–	–	–	Ever exposed to APFO	52	SMR = 0.75	0.56, 0.98	Respiratory	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Larynx	–	–	–	–	–	–	–	–	Ever exposed to APFO	2	SMR = 0.76	0.09, 2.75	Larynx	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Lung	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	12 16 32 24 84 84	SMR = 0.58 SMR = 0.63 SMR = 1.09 SMR = 0.75 SMR = 0.78 SMR = 0.60	0.30, 1.02 0.36, 1.02 0.35, 1.54 0.48, 1.11 0.62, 1.64 0.48, 0.74	Per unit of logged cumulative serum PFOA (ng/mL)	108 95 community 13 workers	HR = 0.88 (no lag) HR = 0.92 (10-yr lag)	0.78, 1.00 (no lag) 0.81, 1.04 (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	10 (3 low TFE) 20 (16 low TFE) 16 (1 low TFE) 13 (0 low TFE) 49	SMR = 0.75 (0.61 low TFE) SMR = 0.91 (0.91 low TFE) SMR = 0.75 (0.55 low TFE) SMR = 0.54 (0.00 low TFE) P-trend = 0.34 SMR = 0.73	0.36, 1.39 (0.13, 1.77 low TFE) 0.56, 1.41 (0.52, 1.47 low TFE) 0.43, 1.22 (0.01, 3.09 low TFE) 0.29, 0.93 (NR low TFE) 0.54, 0.97	Lung	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	632 313 23 90 84 85 37 91 95 78 29	OR = 1.2 OR = 1.3 OR = 1.1 OR = 1.1 OR = 1.3 OR = 1.1 OR = 1.0 OR = 1.0 OR = 1.0 OR = 1.2 OR = 1.0	1.1, 1.3 1.1, 1.5 0.7, 1.8 0.9, 1.4 1.0, 1.7 0.8, 1.4 0.7, 1.5 0.7, 1.2 0.8, 1.3 0.9, 1.6 0.7, 1.6	–	–	–	–	–	–	–	–	–	–	–	–
Other respiratory	–	–	–	–	–	–	–	–	–	–	–	–	Other respiratory	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Mesothelioma	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US With 10-yr lag: 0–< 798 ppm-yrs 798–< 1,379 ppm-yrs 1,379–< 2,384 ppm-yrs ≥ 2,384 ppm-yrs	0 0 1 5 6 6 0 0 2 4	SMR = 0.00 SMR = 0.00 SMR = 1.73 SMR = 6.27 P-trend = 0.02 SMR = 2.85 SMR = 4.83 SMR = 0.00 SMR = 0.00 SMR = 3.08 SMR = 4.66 P-trend = 0.15	0.00, 15.40 0.00, 7.51 0.04, 9.65 2.04, 14.63 1.05, 6.20 1.77, 10.52 0.00, 17.8 0.00, 9.55 0.37, 1.12 1.27, 11.93	–	–	–	–	–	–	–	–	Mesothelioma	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Breast	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	2 0 1 0 4	SMR = 1.49 SMR = 0.00 SMR = 0.87 SMR = 0.00 SMR = 0.65 SMR = 0.79	0.18, 5.39 0.00, 3.56 0.02, 4.83 0.00, 3.42 0.13, 1.90 0.21, 2.02	Per unit of logged cumulative serum PFOA (ng/mL)	559 546 community 13 workers	HR = 0.94 (no lag) HR = 0.93 (10-yr lag)	0.89, 1.00 (no lag) 0.88, 0.99 (10-yr lag)	–	–	–	–	Breast	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	436 193 18 73 50 69 33 72 77 45 29	OR = 1.0 OR = 1.0 OR = 0.8 OR = 1.1 OR = 0.7 OR = 1.2 OR = 1.2 OR = 0.9 OR = 1.1 OR = 0.7 OR = 1.4	0.9, 1.1 0.8, 1.2 0.5, 1.5 0.8, 1.5 0.5, 1.1 0.9, 1.7 0.8, 2.0 0.7, 1.2 0.8, 1.5 0.5, 1.0 0.9, 2.3	–	–	–	–	–	–	–	–	–	–	–	–
Genitourinary	–	–	–	–	–	–	–	–	Ever exposed to APFO	17	SMR = 0.69	0.40, 1.10	Genitourinary	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Female genital	–	–	–	–	–	–	–	–	–	–	–	–	Female genital	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Ovary	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	43 43 community 0 workers	HR = 0.95 (no lag) HR = 0.90 (10-yr lag)	0.76, 1.19 (no lag) 0.69, 1.16 (10-yr lag)	–	–	–	–	Ovary	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA 3.8–88 μg/L-yr PFOA 89–197 μg/L-yr PFOA 198–599 μg/L-yr PFOA 600–4,679 μg/L-yr PFOA	48 19 2 11 6 5 5 4 10 8 5 NR NR NR NR	OR = 1.0 OR = 0.9 OR = 1.1 OR = 1.6 OR = 1.1 OR = 0.7 OR = 1.8 OR = 0.5 OR = 1.4 OR = 1.4 OR = 2.1 OR = 0.7 OR = 0.9 OR = 1.7 OR = 2.2	0.8, 1.4 0.5, 1.4 0.3, 4.4 0.9, 3.0 0.5, 2.4 0.3, 1.7 0.7, 4.4 0.2, 1.4 0.7, 2.7 0.7, 2.9 0.8, 5.5 0.3, 1.6 0.4, 2.1 0.9, 3.4 0.9, 5.7	–	–	–	–	–	–	–	–	–	–	–	–
Uterus	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	103 96 community 7 workers	HR = 1.05 (no lag) HR = 0.99 (10-yr lag)	0.91, 1.20 (no lag) 0.86, 1.15 (10-yr lag)	–	–	–	–	Uterus	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	97 45 4 14 12 15 7 17 14 12 4	OR = 1.0 OR = 1.1 OR = 0.9 OR = 0.9 OR = 0.9 OR = 1.1 OR = 1.1 OR = 1.2 OR = 0.9 OR = 1.7 OR = 0.7	0.8, 1.3 0.8, 1.5 0.3, 2.4 0.5, 1.6 0.5, 1.6 0.6, 1.9 0.5, 2.4 0.8, 1.7 0.6, 1.3 1.2, 2.5 0.3, 1.5	–	–	–	–	–	–	–	–	–	–	–	–
Cervix	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	22 21 community 1 worker	HR = 0.89 (no lag) HR = 0.98 (10-yr lag)	0.63, 1.24 (no lag) 0.69, 1.38 (10-yr lag)	–	–	–	–	Cervix	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	35 11 2 5 8 5 4 11 4 8 2	OR = 0.8 OR = 0.7 OR = 0.9 OR = 0.6 OR = 1.8 OR = 0.7 OR = 0.9 OR = 1.1 OR = 0.5 OR = 1.7 OR = 0.6	0.6, 1.2 0.4, 1.3 0.2, 4.1 0.2, 1.6 0.8, 3.8 0.3, 1.7 0.3, 2.9 0.6, 2.2 0.2, 1.5 0.8, 3.8 0.1, 2.6	–	–	–	–	–	–	–	–	–	–	–	–
Other female genital	–	–	–	–	–	–	–	–	–	–	–	–	Other female genital	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Male genital	–	–	–	–	–	–	–	–	–	–	–	–	Male genital	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Prostate	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	6 6 5 4 21 21	SMR = 1.07 SMR = 0.82 SMR = 0.65 SMR = 0.57 SMR = 0.76 SMR = 0.72	0.39, 2.34 0.30, 1.78 0.21, 1.51 0.16, 1.46 0.47, 1.16 0.45, 1.10	Per unit of logged cumulative serum PFOA (ng/mL)	446 317 community 129 workers	HR = 0.99 (no lag) HR = 0.99 (10-yr lag)	0.93, 1.04 (no lag) 0.94, 1.05 (10-yr lag)	Ever exposed to APFO	3	SMR = 0.24	0.05, 0.70	Prostate	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA 3.8–88 μg/L-yr PFOA 89–197 μg/L-yr PFOA 198–599 μg/L-yr PFOA 600–4,679 μg/L-yr PFOA	434 196 12 56 56 78 36 71 65 47 31 NR NR NR NR	OR = 0.9 OR = 0.9 OR = 1.3 OR = 0.8 OR = 0.8 OR = 1.2 OR = 1.4 OR = 1.1 OR = 0.8 OR = 0.8 OR = 1.5 OR = 1.1 OR = 0.8 OR = 0.8 OR = 1.5	0.8, 1.1 0.7, 1.0 0.6, 2.6 0.6, 1.1 0.6, 1.1 0.9, 1.6 0.9, 2.3 0.8, 1.5 0.6, 1.0 0.5, 1.1 0.9, 2.5 0.8, 1.5 0.6, 1.0 0.6, 1.1 0.9, 2.5	–	–	–	–	PFOA ≤ 1.9 ng/mL (control median) PFOA > 1.9 ng/mL PFOA > 1.9 ng/mL, Gleason score 2–6 PFOA > 1.9 ng/mL, Gleason score 2–7 PFOA > 1.9 ng/mL, PSA ≤ 10 ng/mL PFOA > 1.9 ng/mL, PSA ≥ 11 ng/mL PFOA ≤ 1.9 ng/mL, no family history PFOA > 1.9 ng/mL, no family history PFOA ≤ 1.9 ng/mL, family history PFOA > 1.9 ng/mL, family history	93 108 37 67 56 52 77 16 84 24	OR = 1.0 OR = 1.1 OR = 1.1 OR = 1.2 OR = 1.0 OR = 1.3 OR = 1.0 OR = 1.1 OR = 1.0 OR = 2.6	Referent 0.7, 1.7 0.6, 2.0 0.7, 1.8 0.6, 1.7 0.8, 2.1 Referent 0.5, 2.6 0.6, 1.5 1.2, 6.0	–	–	–	–
Testis (with or without other male genital)	All vs. DuPont region All vs. US	1 1	SMR = 1.80 SMR = 0.74	0.05, 10.03 0.02, 4.12	Per unit of logged cumulative serum PFOA (ng/mL) Quartiles 2, 3, and 4 vs. quartile 1 of estimated cumulative serum PFOA concentration	17 15 community 2 workers 17 15 community 2 workers	HR = 1.34 overall (no lag) HR = 1.73 in community (no lag) HR = 0.85 in workers (no lag) HR = 1.28 overall (10-yr lag) HR = 1.53 in community (10-yr lag) HR = 1.61 in workers (10-yr lag) Quartile 2: HR = 1.04 overall (no lag) HR = 0.80 in community (no lag) HR = 0.87 overall (10-yr lag) HR = 0.98 in community (10-yr lag) Quartile 3: HR = 1.91 overall (no lag) HR = 3.07 in community (no lag) HR = 1.08 overall (10-yr lag) HR = 1.54 in community (10-yr lag) Quartile 4: HR = 3.17 overall (no lag) HR = 5.80 in community (no lag) HR = 2.36 overall (10-yr lag) HR = 4.66 in community (10-yr lag) P-trend across quartiles: 0.04 overall, 0.05 in community with no lag P-trend across quartiles: 0.02 overall, 0.02 in community with 10-yr lag	1.00, 1.79 overall (no lag) 1.24, 2.40 in community (no lag) 0.04, 19.7 in workers (no lag) 0.95, 1.73 overall (10-yr lag) 1.09, 2.15 in community (10-yr lag) 0.21, 12.20 in workers (10-yr lag) Quartile 2: 0.26, 4.22 overall (no lag) 0.16, 3.97 in community (no lag) 0.15, 4.88 overall (10-yr lag) 0.13, 7.14 in community (10-yr lag) Quartile 3: 0.47, 7.75 overall (no lag) 0.61, 15.36 in community (no lag) 0.20, 5.90 overall (10-yr lag) 0.19, 12.21 in community (10-yr lag) Quartile 4: 0.75, 13.45 overall (no lag) 0.97, 34.58 in community (no lag) 0.41, 13.65 overall (10-yr lag) 0.52, 41.63 in community (10-yr lag)	Ever exposed to APFO	1	SMR = 1.35	0.03, 7.49	Testis (with or without other male genital)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA 3.8–88 μg/L-yr PFOA 89–197 μg/L-yr PFOA 198–599 μg/L-yr PFOA 600–4,679 μg/L-yr PFOA	18 5 0 1 2 2 8 1 3 1 6 NR NR NR NR	OR = 1.0 OR = 0.5 OR = NR OR = 0.6 OR = 0.4 OR = 0.9 OR = 5.1 OR = 0.2 OR = 0.6 OR = 0.3 OR = 2.8 OR = 0.4 OR = 0.4 OR = 0.4 OR = 2.8	0.6, 1.8 0.2, 1.5 NR 0.1, 5.0 0.1, 2.0 0.2, 4.5 1.6, 15.6 0.0, 1.6 0.2, 2.2 0.0, 2.7 0.8, 9.2 0.1, 1.9 0.1, 1.8 0.0, 2.9 0.8, 9.6	–	–	–	–	–	–	–	–	–	–	–	–
Other male genital	–	–	–	–	–	–	–	–	–	–	–	–	Other male genital	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Urinary	–	–	–	–	–	–	–	–	–	–	–	–	Urinary	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Kidney (with or without other urinary)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US With 10-yr lag: 0–< 798 ppm-yrs 798–< 1,379 ppm-yrs 1,379–< 2,384 ppm-yrs ≥ 2,384 ppm-yrs With 20-year lag: Quartile 1 Quartile 2 Quartile 3 Quartile 4	1 3 0 8 12 12 2 2 1 7 15 (including contributing causes)	SMR = 1.07 SMR = 1.37 SMR = 0.00 SMR = 2.66 P-trend = 0.02 SMR = 1.28 SMR = 1.09 SMR = 1.05 SMR = 0.87 SMR = 0.44 SMR = 2.82 P-trend = 0.02 SMR = 1.08 SMR = 0.73 SMR = 0.41 SMR = 3.54 P-trend = 0.003	0.02, 3.62 0.28, 3.99 0.00, 1.42 1.15, 5.24 0.66, 2.24 0.56, 1.90 0.13, 3.79 0.11, 3.15 0.01, 2.44 1.13, 5.81 NR NR NR NR	Per unit of logged cumulative serum PFOA (ng/mL) Quartiles 2, 3, and 4 vs. quartile 1 of estimated cumulative serum PFOA concentration	105 87 community 18 workers 105 87 community 18 workers	HR = 1.10 overall (no lag) HR = 1.14 in community (no lag) HR = 0.95 in workers (no lag) HR = 1.09 overall (10-yr lag) HR = 1.11 in community (10-yr lag) HR = 0.99 in workers (10-yr lag) Quartile 2: HR = 1.23 overall (no lag) HR = 1.34 in community (no lag) HR = 0.84 in workers (no lag) HR = 0.99 overall (10-yr lag) HR = 0.94 in community (10-yr lag) HR = 1.22 in workers (10-yr lag) Quartile 3: HR = 1.48 overall (no lag) HR = 1.95 in community (no lag) HR = 4.20 in workers (no lag) HR = 1.69 overall (10-yr lag) HR = 1.08 in community (10-yr lag) HR = 3.27 in workers (10-yr lag) Quartile 4: HR = 1.58 overall (no lag) HR = 2.04 in community (no lag) HR = 0.83 in workers (no lag) HR = 1.43 overall (10-yr lag) HR = 1.50 in community (10-yr lag) HR = 0.99 in workers (10-yr lag)P-trend across quartiles: 0.18 overall, 0.20 in community, and 0.54 in workers with no lag P-trend across quartiles: 0.34 overall, 0.02 in community, and 0.42 in workers with 10-yr lag	0.98, 1.24 overall (no lag) 0.99, 1.32 in community (no lag) 0.59, 1.52 in workers (no lag) 0.97, 1.21 overall (10-yr lag) 0.96, 1.29 in community (10-yr lag) 0.67, 1.46 in workers (10-yr lag) Quartile 2: 0.70, 2.17 overall (no lag) 0.71, 2.52 in community (no lag) 0.21, 3.40 in workers (no lag) 0.53, 1.85 overall (10-yr lag) 0.45, 1.99 in community (10-yr lag) 0.28, 5.30 in workers (10-yr lag) Quartile 3: 0.84, 2.60 overall (no lag) 1.03, 3.70 in community (no lag) 1.07, 16.44 in workers (no lag) 0.93, 3.07 overall (10-yr lag) 0.52, 2.25 in community (10-yr lag) 0.76, 14.10 in workers (10-yr lag) Quartile 4: 0.88, 2.84 overall (no lag) 1.07, 3.88 in community (no lag) 0.20, 3.55 in workers (no lag) 0.76, 2.69 overall (10-yr lag) 0.72, 3.13 in community (10-yr lag) 0.21, 4.68 in workers (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	0 (0 low TFE) 3 (2 low TFE) 3 (0 low TFE) 4 (0 low TFE) 10	SMR = 0.00 (0.00 low TFE) SMR = 1.57 (1.28 low TFE) SMR = 1.50 (0.00 low TFE) SMR = 2.00 (0.00 low TFE) P-trend = 0.28 SMR = 1.69	NR (NR low TFE) 0.32, 4.59 (0.16, 4.63 low TFE) 0.31, 4.39 (NR low TFE) 0.54, 5.12 (NR low TFE) 0.81, 3.11	Kidney (with or without other urinary)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA 3.8–88 μg/L-yr PFOA 89–197 μg/L-yr PFOA 198–599 μg/L-yr PFOA 600–4,679 μg/L-yr PFOA	94 35 0 17 23 9 10 11 17 22 9 (6 F; 3 M) NR NR NR NR	OR = 1.1 OR = 0.9 OR = NR OR = 1.4 OR = 2.0 OR = 0.7 OR = 1.7 OR = 0.8 OR = 1.2 OR = 2.0 OR = 2.0 (3.5 F; 1.0 M) OR = 0.8 OR = 1.2 OR = 2.0 OR = 2.1	0.9, 1.4 0.6, 1.3 NR 0.8, 2.3 1.3, 3.1 0.4, 1.3 0.9, 3.3 0.4, 1.5 0.7, 2.0 1.3, 3.2 1.0, 3.9 (1.6, 15.6 F; 0.3, 3.4 M) 0.4, 1.5 0.7, 2.0 1.3, 3.2 1.1, 4.2	–	–	–	–	–	–	–	–	–	–	–	–
Bladder (with or without other urinary)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	2 6 1 1 10 10	SMR = 1.24 SMR = 2.49 SMR = 0.39 SMR = 0.36 SMR = 1.08 SMR = 0.95	0.15, 4.47 0.97, 5.78 0.01, 2.17 0.10, 2.01 0.52, 1.99 0.46, 1.75	Per unit of logged cumulative serum PFOA (ng/mL)	105 76 community 29 workers	HR = 1.00 (no lag) HR = 0.98 (10-yr lag)	0.89, 1.12 (no lag) 0.88, 1.10 (10-yr lag)	Ever exposed to APFO	3	SMR = 0.55	0.11, 1.60	Bladder (with or without other urinary)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	137 58 4 24 20 24 7 23 21 21 4	OR = 0.8 OR = 0.7 OR = 0.8 OR = 1.1 OR = 0.9 OR = 1.0 OR = 0.6 OR = 0.9 OR = 0.9 OR = 1.2 OR = 0.6	0.7, 1.0 0.6, 1.0 0.3, 2.1 0.7, 1.6 0.6, 1.5 0.6, 1.5 0.3, 1.4 0.6, 1.4 0.6, 1.4 0.8, 2.0 0.2, 1.5	–	–	–	–	–	–	–	–	–	–	–	–
Malignant melanoma	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	241 200 community 41 workers	HR = 1.00 (no lag) HR = 1.04 (10-yr lag)	0.92, 1.09 (no lag) 0.96, 1.13 (10-yr lag)	–	–	–	–	Malignant melanoma	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	168 61 4 38 21 32 12 27 38 21 9	OR = 0.9 OR = 0.7 OR = 0.9 OR = 1.4 OR = 0.9 OR = 1.2 OR = 1.0 OR = 1.2 OR = 1.3 OR = 1.0 OR = 0.9	0.8, 1.1 0.5, 0.9 0.3, 2.5 1.0, 2.0 0.6, 1.4 0.8, 1.7 0.6, 1.9 0.8, 1.8 0.9, 1.8 0.6, 1.5 0.5, 1.9	–	–	–	–	–	–	–	–	–	–	–	–
Soft tissue	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	15 13 community 2 workers	HR = 0.75 (no lag) HR = 0.72 (10-yr lag)	0.51, 1.10 (no lag) 0.48, 1.09 (10-yr lag)	–	–	–	–	Soft tissue	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Brain/central nervous system	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL)	17 13 community 4 workers	HR = 1.13 (no lag) HR = 1.06 (10-yr lag)	0.84, 1.51 (no lag) 0.79, 1.41 (10-yr lag)	Ever exposed to APFO	4	SMR = 0.59	0.16, 1.51	Brain/central nervous system	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	60 29 3 11 9 7 1 12 16 4 0	OR = 1.0 OR = 1.1 OR = 1.7 OR = 1.2 OR = 1.1 OR = 0.8 OR = 0.2 OR = 1.5 OR = 1.8 OR = 0.6 OR = NR	0.8, 1.3 0.7, 1.6 0.5, 5.4 0.6, 2.2 0.5, 2.1 0.4, 1.8 0.0, 1.5 0.8, 2.7 1.1, 3.2 0.2, 1.6 NR	–	–	–	–	–	–	–	–	–	–	–	–
Thyroid (with or without other endocrine)	–	–	–	–	Per unit of logged cumulative serum PFOA (ng/mL) Quartiles 2, 3, and 4 vs. quartile 1 of estimated cumulative serum PFOA concentration	86 78 community 8 workers 86 78 community 8 workers	HR = 1.10 overall (no lag) HR = 1.04 in community (no lag) HR = 1.93 in workers (no lag) HR = 1.04 overall (10-yr lag) HR = 1.00 in community (10-yr lag) HR = 1.12 in workers (10-yr lag) Quartile 2: HR = 1.54 overall (no lag) HR = 1.54 in community (no lag) HR = 4.64 in workers (no lag) HR = 2.06 overall (10-yr lag) HR = 2.09 in community (10-yr lag) HR = 1.65 in workers (10-yr lag) Quartile 3: HR = 1.48 overall (no lag) HR = 1.71 in community (no lag) HR = 9.70 in workers (no lag) HR = 2.02 overall (10-yr lag) HR = 1.92 in community (10-yr lag) HR = 4.52 in workers (10-yr lag)	0.95, 1.26 overall (no lag) 0.89, 1.23 in community (no lag) 1.00, 3.71 in workers (no lag) 0.89, 1.20 overall (10-yr lag) 0.84, 1.20 in community (10-yr lag) 0.61, 2.05 in workers (10-yr lag) Quartile 2: 0.77, 3.12 overall (no lag) 0.73, 3.26 in community (no lag) 0.42, 50.8 in workers (no lag) 0.93, 4.56 overall (10-yr lag) 0.91, 4.82 in community (10-yr lag) 0.09, 31.5 in workers (10-yr lag) Quartile 3: 0.74, 2.93 overall (no lag) 0.81, 3.59 in community (no lag) 0.67, 141.2 in workers (no lag) 0.90, 4.52 overall (10-yr lag) 0.82, 4.50 in community (10-yr lag) 0.10, 198.4 in workers (10-yr lag)	–	–	–	–	Thyroid (with or without other endocrine)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	40 23 0 5 2 7 3 5 5 3 2	OR = 1.1 OR = 1.4 OR = NR OR = 0.9 OR = 0.3 OR = 1.2 OR = 0.8 OR = 0.9 OR = 0.9 OR = 0.7 OR = 0.8	0.7, 1.5 0.9, 2.2 NR 0.4, 2.2 0.1, 1.4 0.6, 2.6 0.3, 2.7 0.4, 2.3 0.4, 2.3 0.2, 2.1 0.2, 3.5	–	–	–	–	–	–	–	–	–	–	–	–
Thyroid continued							Quartile 4: HR = 1.73 overall (no lag) HR = 1.40 in community (no lag) HR = 14.72 in workers (no lag) HR = 1.51 overall (10-yr lag) HR = 1.42 in community (10-yr lag) HR = 5.85 in workers (10-yr lag) P-trend across quartiles: 0.25 overall, 0.46 in community, and 0.04 in workers with no lag P-trend across quartiles: 0.57 overall, 0.56 in community, and 0.01 in workers with 10-yr lag	Quartile 4: 0.85, 3.54 overall (no lag) 0.66, 2.97 in community (no lag) 0.85, 253.9 in workers (no lag) 0.67, 3.39 overall (10-yr lag) 0.60, 3.37 in community (10-yr lag) 0.13, 257.1 in workers (10-yr lag)
Bone	–	–	–	–	–	–	–	–	–	–	–	–	Bone	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Lymphatic and hematopoietic	–	–	–	–	–	–	–	–	Ever exposed to APFO	19	SMR = 1.04	0.62, 1.62	Lymphatic and hematopoietic	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Non-Hodgkin lymphoma (with or without Hodgkin lymphoma)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	4 3 3 4 14 14	SMR = 1.54 SMR = 0.99 SMR = 0.85 SMR = 0.96 SMR = 1.05 SMR = 0.79	0.42, 3.95 0.20, 2.88 0.17, 2.48 0.26, 2.46 0.57, 1.76 0.42, 1.35	Per unit of logged cumulative serum PFOA (ng/mL)	136 121 community 15 workers	HR = 1.01 (no lag) HR = 0.98 (10-yr lag)	0.91, 1.12 (no lag) 0.88, 1.10 (10-yr lag)	Ever exposed to APFO	5	SMR = 0.79	0.26, 1.84	Non-Hodgkin lymphoma (with or without Hodgkin lymphoma)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA 3.8–88 μg/L-yr PFOA 89–197 μg/L-yr PFOA 198–599 μg/L-yr PFOA 600–4,679 μg/L-yr PFOA	152 68 5 24 21 20 14 20 28 17 11 NR NR NR NR	OR = 1.2 OR = 1.2 OR = 1.1 OR = 1.3 OR = 1.2 OR = 1.1 OR = 1.6 OR = 1.0 OR = 1.5 OR = 1.1 OR = 1.8 OR = 1.0 OR = 1.5 OR = 1.0 OR = 2.0	1.0, 1.5 0.9, 1.5 0.4, 2.7 0.9, 2.0 0.8, 1.9 0.7, 1.7 0.9, 2.8 0.6, 1.6 1.0, 2.2 0.7, 1.7 1.0, 3.4 0.6, 1.6 1.0, 2.2 0.6, 1.7 1.0, 3.7	–	–	–	–	–	–	–	–	–	–	–	–
Hodgkin lymphoma	–	–	–	–	–	–	–	–	–	–	–	–	Hodgkin lymphoma	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Multiple myeloma	–	–	–	–	–	–	–	–	Ever exposed to APFO	2	SMR = 0.66	0.08, 2.39	Multiple myeloma	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	36 20 1 7 3 4 1 7 6 4 1	OR = 1.1 OR = 1.4 OR = 0.9 OR = 1.5 OR = 0.7 OR = 0.9 OR = 0.5 OR = 1.4 OR = 1.1 OR = 1.0 OR = 0.6	0.8, 1.6 0.9, 2.2 0.1, 6.6 0.7, 3.2 0.2, 2.2 0.3, 2.3 0.1, 3.6 0.7, 3.2 0.5, 2.6 0.3, 2.7 0.1, 4.7	–	–	–	–	–	–	–	–	–	–	–	–
Leukemia (with or without aleukemia)	0–< 904 ppm-yrs 904–< 1,520 ppm-yrs 1,520–< 2,700 ppm-yrs ≥ 2,700 ppm-yrs All vs. DuPont region All vs. US	1 7 2 4 14 14	SMR = 0.28 SMR = 2.34 SMR = 0.57 SMR = 1.03 SMR = 1.05 SMR = 0.88	0.01, 1.59 0.94, 4.81 0.07, 2.05 0.28, 2.63 0.57, 1.76 0.48, 0.47 [sic]	Per unit of logged cumulative serum PFOA (ng/mL)	66 53 community 13 workers	HR = 1.01 (no lag) HR = 1.02 (10-yr lag)	0.87, 1.18 (no lag) 0.88, 1.18 (10-yr lag)	Never exposed to APFO Low cumulative APFO (< 16 unit-yrs) Medium cumulative APFO (16–138 unit-yrs) High cumulative APFO (≥ 139 unit-yrs) Ever exposed to APFO	1 (0 low TFE) 4 (4 low TFE) 3 (0 low TFE) 4 (0 low TFE) 11	SMR = 0.79 (0.00 low TFE) SMR = 1.64 (1.99 low TFE) SMR = 1.35 (0.00 low TFE) SMR = 1.85 (0.00 low TFE) P-trend = 0.58 SMR = 1.61	0.02, 4.40 (NR low TFE) 0.45, 4.20 (0.54, 5.10 low TFE) 0.28, 3.94 (NR low TFE) 0.50, 4.74 (NR low TFE) 0.80, 2.88	Leukemia (with or without aleukemia)	Contaminated districts Mason water district Pomeroy water district Belpre water district Tuppers Plains district Lubeck water district Little Hocking district 3.7–12.8 μg/L PFOA 12.9–30.7 μg/L PFOA 30.8–109 μg/L PFOA 110–655 μg/L PFOA	72 34 1 12 9 11 5 14 12 8 2	OR = 0.9 OR = 0.9 OR = 0.4 OR = 1.0 OR = 0.8 OR = 0.9 OR = 1.0 OR = 1.2 OR = 1.0 OR = 0.9 OR = 0.6	0.7, 1.1 0.6, 1.3 0.1, 2.8 0.6, 1.9 0.4, 1.7 0.5, 1.6 0.4, 2.3 0.7, 2.1 0.6, 1.9 0.4, 1.8 0.1, 2.3	–	–	–	–	–	–	–	–	–	–	–	–
Other lymphopoietic	–	–	–	–	–	–	–	–	–	–	–	–	Other lymphopoietic	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Other malignant neoplasms	–	–	–	–	–	–	–	–	–	–	–	–	Other malignant neoplasms	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–	–

Abbreviations: APFO: ammonium perfluorooctanoate; CI: confidence interval; HCC: hepatocellular carcinoma; HR: hazard ratio; NR: not reported; NR: not reported; OR: odds ratio; PFOA (C8): perfluorooctanoic acid; PSA: prostate-specific antigen; RR: rate ratio or relative risk; SD: standard deviation; SMR: standardized mortality ratio; TFE: tetrafluoroethylene.

Table 3. Design of epidemiologic studies of perfluorooctanesulfonate (PFOS) and cancer.

Reference	Study location	Study design	Study subjects	Comparison subjects	Follow-up	Exposure assessment	Outcome assessment	Adjustment factors	Comments
Alexander et al. 2003	Decatur, Alabama, United States	Retrospective cohort mortality	2,083 manufacturing facility workers employed for ≥ 1 year in a chemical plant and/or film plant before 1998	Alabama state population (Caucasians) 23 regional county populations in sensitivity analysis	1961–1997 through 1998; median = 25.9 years	Relative PFOS exposure estimated by a job-exposure matrix based on cohort work history records and a 1998 assessment of serum PFOS by job in 232 employees Geometric mean serum PFOS = 0.9 ppm (95% CI: 0.8, 1.1) in chemical plant employees, including cell operators (2.0 ppm), waste operators (1.5 ppm), chemical operators (1.5 ppm), maintenance workers (1.3 ppm), supervisors/managers (0.9 ppm), mill operators (0.6 ppm), engineer/lab workers (0.4 ppm), and administrative assistants (0.4 ppm); 0.1 ppm (95% CI: 0.1, 0.1) in film plant employees	Vital records searches, with death certificate review for 96% of decedents	Age, sex, and calendar period	Exposure to other fluorochemicals, including PFOA, was possible at the manufacturing facility. Geometric mean serum PFOA in chemical plant employees = 0.899 ppm (95% CI: 0.722, 1.120) (Olsen et al. 2003); correlated with serum PFOS levels
Olsen et al. 2004	Decatur, Alabama, United States	Retrospective cohort	1,311 workers (652 in the fluorochemical production chemical plant, including 211 with high-exposure jobs for ≥ 10 years before study entry; 659 in the film plant, including 345 with similar jobs for ≥ 10 years before study entry) employed for ≥ 1 year at a manufacturing facility as of 1 January 1993.	Expected number of claims calculated based on the remainder of the 3M manufacturing population based in the United States (− 20,000 workers)	1993 through 1998	Examination of computerized work history record to determine whether each employee had 1) ever worked in the chemical plant, film plant, or both; 2) worked in the chemical plant, film plant, or both during the study period; and 3) worked continuously in either plant for the entire 10 years before study entry in 1993. Chemical plant job titles characterized as having potentially higher or lower PFOS exposure based on geometric mean serum PFOS concentrations (as in Alexander et al. 2003)	Medical and prescription claims grouped into “episodes of care” = constellation of 1 or more claims data records categorized based on diagnoses and procedures grouped within each episode and defined by ICD diagnosis, revenue, current procedural technology codes from facility and professional claims, and National Drug Codes from pharmacy claims, with software using logic to determine the diagnosis code most likely to be the reason for the encounter RR estimated as ratio of two indirectly standardized estimates comparing chemical plant workers with film plant workers	Age and sex	0.5 deaths were considered observed episodes of care in the film plant to calculate SIR ratios for melanoma in the comparison of chemical vs. film plant workers, and for colon cancer, rectal cancer, and melanoma in the comparison of long-term chemical vs. film plant workers “We are aware that in 1997 there was a heightened awareness for colon cancer screening among chemical plant employees.” (p.844)
Alexander et al. 2007	Decatur, Alabama, United States	Retrospective cohort	Same as Alexander et al. 2003	U.S. population and internal referent	1961–1997 through 2002	Same as Alexander et al. 2003	Vital records searches, with death certificate review for 98% of 188 decedents (5 with bladder cancer as underlying cause of death) For 1,895 living cohort members, case ascertainment by self-report on mailed questionnaire (N = 1,138) or telephone (N = 262), followed by a request for medical records verification of reported diagnoses (6 self-reported bladder cancer cases; 2 confirmed, 4 without consent for confirmation)	Age, sex, and calendar period for SIRs Age and sex for RRs	5 (83%) of 6 living bladder cancer cases and 56% of noncases reported a history of cigarette smoking. Smoking prevalence = 60% and 62% in two upper quartiles of cumulative PFOS exposure vs. 52% and 52% in two lower quartiles
Grice et al. 2007	Decatur, Alabama, United States	Case-control	Cancer cases among 1,400 workers (of 1,895 eligible; 1,137 male, 263 female) employed for ≥ 1 year at a facility that manufactured POSF-based chemicals and specialty films Also included cancers reported on death certificates of 188 decedents	Noncases in same worker population	None; ascertainment period = 1961 through 2002	Same as Alexander et al. 2003 Geometric mean serum PFOS concentrations (ppm) by workplace exposure category: No direct exposure: 0.11–0.29 Low potential exposure: 0.39–0.89 High potential exposure: 1.30–1.97	Same as Alexander et al. 2007 Self-administered questionnaire on various diseases and conditions, with medical records sought to validate self-reported diagnoses of prostate cancer (22 confirmed of 29 reported), colon cancer (12 confirmed of 22 reported), breast cancer (NR confirmed of 4 reported), and melanoma (8 confirmed of 39 reported) Vital records searches, with death certificate review for 98% of 188 decedents	Age and sex	Analyses are of self-reported colon and prostate cancers and validated melanoma Colon and prostate cancers not validated were due to lack of consent (N = 10 colon, N = 6 prostate) or unretrievable medical records (N = 1 colon, N = 1 prostate); melanomas not validated were due to lack of consent/records (N = 17), records showing nonmelanoma skin cancer (N = 12), or records showing noncancerous lesion (N = 2)
Eriksen et al. 2009	Denmark	Prospective case-cohort	713 prostate cancer cases, 332 bladder cancer cases, 128 pancreatic cancer cases, and 67 liver cancer cases diagnosed after enrollment in a prospective cohort of 57,053 Danish-born adults aged 50–65 years with no prior cancer	680 men and 92 women without cancer randomly selected from the same prospective cohort	1993–1997 to 2006 Cancers diagnosed 0–12 years (median: 7 years) after cohort enrollment	Plasma PFOA and PFOS measured in samples taken at cohort entry Median (5th–95th percentile) PFOS, ng/mL Prostate cancer: 36.8 (18.2–62.5) Bladder cancer: 32.3 (15.2–58.0) Pancreatic cancer: 32.7 (15.2–56.4) Liver cancer: 31.0 (15.8–62.9) Noncancer men: 35.0 (16.8–62.4) Noncancer women: 29.3 (14.2–55.6)	Linkage to Danish Cancer Registry and Danish Pathology Data Bank	Age as time scale (all sites), education (prostate, bladder, liver), body mass index (prostate), dietary fat intake (prostate, pancreas), fruit and vegetable intake (prostate, pancreas), smoking status (bladder, pancreas, liver), smoking intensity (bladder, pancreas), smoking duration (bladder, pancreas), high-risk occupation (bladder, liver), alcohol intake (liver); hazards stratified by sex where appropriate	Spearman ρ = 0.70 for correlation between PFOA and PFOS
Vassiliadou et al. 2010	Athens and Argolida, Greece	Cross-sectional	40 cancer patients hospitalized at the Saint Savas Anticancer Hospital in Athens	56 healthy working employees at a research center undergoing their annual health check at the Medical Care Center of NCSR “Demokritos” in Athens (urban area) 86 ambulatory patients and healthy individuals undergoing a medical check at the General Hospital of Nafplio, Argolida (semi-urban/rural area)	None; blood samples collected in first half of 2009	PFOA and PFOS measured in serum	Cancer cases hospitalized with malignancy; noncancer controls undergoing routine medical examination	None	–
Bonefeld-Jorgensen et al. 2011	Nuuk, Greenland	Case-control	31 Greenland Inuit women with breast cancer (80% of all breast cancer cases in Greenland during sampling period) identified from Dronning Ingrids Hospital	115 (98 with data on PFOA and PFOS) Greenland Inuit women without breast cancer frequency-matched to cases on age and district, identified from two cross-sectional serological studies in randomly sampled women, with participation rates > 90% (Cote et al. 2006; Deutch et al. 2007)	None; sampling period: 2000–2003	10 perfluorinated compounds including PFOA and PFOS measured in serum from cases at breast cancer diagnosis and from controls at study enrollment Serum PFOS (ng/mL) Cases: median: 45.6; 95% CI: 45.7, 69.3; range: 11.6–124 Controls: median: 21.9; 95% CI: 31.1, 46.0; range: 1.5–172	Cases identified from a single hospital where all breast cancer cases in Greenland are registered	Adjusted models: age, body mass index, full-term pregnancies, cotinine, breastfeeding, and menopausal status	Also measured polychlorinated biphenyl congeners, organochlorine compounds, lipids, and fatty acids in plasma; metals in whole blood; and cotinine, estradiol, and xenobiotic-induced transactivity of estrogen receptor, androgen receptor, and aryl hydrocarbon receptor in serum
Yeung et al. 2013	Melbourne, Australia	Cross-sectional	66 diseased liver tissues (12 HCC [24 serum specimens]; 14 HCC with HCV [13 serum specimens]; 38 cirrhosis with HCV [38 serum specimens]; 2 amyloidosis or acute liver failure [4 serum specimens]) obtained from explanted livers at the time of liver transplantation at a single liver transplant unit	9 histologically normal control liver tissues (25 serum samples) obtained from patients resected for colorectal metastasis, with specimens taken well clear of the tumor margin	None; case tissues and serum specimens obtained from 2004 through 2009, control tissues and serum specimens mostly obtained from 2007 through 2008	12 perfluoroalkyl and polyfluoroalkyl substances measured in liver and serum specimens	Liver disease cases identified from the liver tissue bank at the Victorian Liver Transplant Unit	None	Spearman ρ = −0.064 for correlation of PFOS in paired serum and liver tissue samples in HCC without HCV; 0.503 in HCC with HCV; 0.699 (P < 0.05) in HCV cirrhosis Spearman ρ = 0.850 for correlation of PFOA and PFOS in control liver tissue; 0.708 in control serum
Hardell et al. 2014	Örebro, Sweden	Case-control	201 incident cases of prostate cancer with blood results, including 200 admitted for treatment at an oncology department at a single hospital in 2007–2011 + 2 previously untreated cases diagnosed during study period and identified from the control group – 1 without blood results; 79% participation rate	185 population controls without prior cancer individually matched to cases on age and county of residence, identified from Swedish population registry with one round of replacement; 60% participation rate, 54% after excluding those with prior cancer	None; enrollment period: 2007–2011	8 perfluorinated compounds including PFOA and PFOS measured in whole blood collected during same time period for cases and controls Whole blood PFOS (ng/mL) Cases: mean: 11; median: 9.0; range: 1.4–69 Controls: mean: 10; median: 8.3; range: 1.7–49	Consecutive, newly diagnosed patients with prostate cancer admitted for treatment with radiation or chemotherapy at the Department of Oncology at the University Hospital in Örebro	Age, body mass index, and year of blood sampling	–
Innes et al. 2014	Mid-Ohio Valley, Ohio and West Virginia, United States	Cross-sectional	208 prevalent cases of colon and/or rectal cancer identified among adults aged ≥ 21 years who lived or worked for ≥ 1 year in one of six contaminated water districts near a chemical plant between 1950 and 3 December 2004, and participated in a baseline health survey, with complete data on all covariates of interest	47,151 adults without cancer from the same study group as the cases	None; survey period: 2005–2006	10 perfluorocarbon compounds including PFOA and PFOS measured in serum collected at the time of the health survey Median serum PFOS = 20.2 ng/mL (range: < 0.5–759.2) Mean ± SD serum PFOS = 23.4 ± 16.3 ng/mL “[S]erum levels of other [perfluoroalkyl acids] for which adequate data were available were comparable to general background levels in the U.S.”	Self-report of colon and/or rectal cancer diagnosis on mailed survey, followed by verification via medical chart review	Age, race, sex, years of education, annual household income, employment status/disability, marital status, smoking status, current alcohol consumption, vegetarian diet, regular exercise program, body mass index, menopausal status, comorbidity, metabolic/physiologic profile (serum lipid profiles, C-reactive protein, estradiol, and uric acid), and gastrointestinal symptoms (diarrhea, abdominal pain, nausea, bloating, blood stools, and indigestion) Further adjustment for other perfluoroalkyl acids, anemia, or diagnosed osteoarthritis, rheumatoid arthritis, and fibromyalgia or exclusion of those with low hemoglobin levels (N = 2,391, including 41 cases) did not alter the results	P-value for interaction = 0.04 for year of diagnosis (stronger inverse association for cases diagnosed in 2000 or later); no significant interaction by sex, body mass index, age, or colorectal cancer treatment method Results were unchanged after restricting the analysis of adults with serum PFOS ≤ 20 ng/mL (N = 23,405 subjects, including 118 cases), excluding primary rectal cancer cases (N = 29), cases undergoing current treatment (N = 21), or those who had received chemotherapy (N = 109), or including unconfirmed self-reported colorectal cancer cases (N = 73)

Abbreviations: CI: confidence interval; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; ICD: International Classification of Diseases; NR: not reported; PFOA (C8): perfluorooctanoic acid; PFOS: perfluorooctanesulfonate; POSF: perfluorooctanesulfonyl fluoride; RR: rate ratio or relative risk; SD: standard deviation; SIR: standardized incidence ratio.

Table 4. Results of epidemiologic studies of perfluorooctanesulfonate (PFOS) and cancer.

	Alexander et al. 2003				Olsen et al. 2004				Alexander et al. 2007				Grice et al. 2007				Eriksen et al. 2009
Organ site	Exposure category	No. deaths	Relative risk	95% CI	Exposure category	No. deaths	Relative risk	95% CI	Organ site	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI	Exposure category	No. cases	Relative risk	95% CI
All sites	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	39 15 6 18 14	SMR = 0.72 SMR = 0.73 SMR = 0.52 SMR = 0.84 SMR = 0.84	0.51, 0.98 0.41, 1.21 0.19, 1.14 0.50, 1.32 0.46, 1.41	–	–	–	–	All sites	–	–	–	–	–	–	–	–	–	–	–	–
Digestive organs and peritoneum	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	5 1 2 2 2	SMR = 0.51 SMR = 0.27 SMR = 0.99 SMR = 0.51 SMR = 0.66	0.17, 1.19 0.01, 1.49 0.12, 3.57 0.06, 1.85 0.08, 2.37	–	–	–	–	Digestive organs and peritoneum	–	–	–	–	–	–	–	–	–	–	–	–
Esophagus	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	2 1 0 1 1	SMR = 1.76 SMR = 2.25 NR SMR = 2.16 SMR = 2.73	0.21, 6.35 0.06, 12.51 NR 0.05, 12.02 0.07, 15.16	–	–	–	–	Esophagus	–	–	–	–	–	–	–	–	–	–	–	–
Colorectum	–	–	–	–	–	–	–	–	Colorectum	–	–	–	–	–	–	–	–	–	–	–	–
Colon	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	1 0 1 0 0	SMR = 0.30 NR SMR = 1.43 NR NR	0.01, 1.66 NR 0.04, 7.94 NR NR	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	4 vs. 1 4 vs. 1.8 3 vs. 0	RR = 5.4 Obs. vs. exp. = 2.2 RR = 12	0.5, > 100 NR 0.8, > 100	Colon	–	–	–	–	Never exposed Ever low or high ≥ 1 year low or high > 1 year high	8 15 14 7	OR = 1.00 OR = 1.21 OR = 1.37 OR = 1.69	Referent 0.51, 2.87 0.57, 3.30 0.68, 4.17	–	–	–	–
Rectum	–	–	–	–	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	4 vs. 3 4 vs. 1.3 3 vs. 0	RR = 1.8 Obs. vs. exp. = 3.1 RR = 11	0.3, 12.4 NR 0.8, > 100	Rectum	–	–	–	–	–	–	–	–	–	–	–	–
Liver (with or without bile ducts)	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	2 0 1 1 1	SMR = 1.61 NR SMR = 3.94 SMR = 2.00 SMR = 2.57	0.20, 5.82 NR 0.10, 21.88 0.05, 11.10 0.06, 14.26	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	0 vs. 1 0 vs. 0.5 0 vs. 1	RR = NR Obs. vs. exp. = 0 RR = NR	NR NR NR	Liver (with or without bile ducts)	–	–	–	–	–	–	–	–	PFOS quartile 1 PFOS quartile 2 PFOS quartile 3 PFOS quartile 4 Per 10 ng/mL plasma PFOS	17 17 17 16 67	RR = 1.00 RR = 0.62 RR = 0.72 RR = 0.59 RR = 0.97	Referent 0.29, 1.33 0.33, 1.56 0.27, 1.27 0.79, 1.19
Pancreas	–	–	–	–	–	–	–	–	Pancreas	–	–	–	–	–	–	–	–	PFOS quartile 1 PFOS quartile 2 PFOS quartile 3 PFOS quartile 4 Per 10 ng/mL plasma PFOS	32 32 32 32 128	RR = 1.00 RR = 1.02 RR = 1.24 RR = 0.91 RR = 0.99	Referent 0.57, 1.84 0.67, 2.31 0.51, 1.65 0.86, 1.14
Respiratory system	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	15 4 4 7 6	SMR = 0.71 SMR = 0.51 SMR = 0.87 SMR = 0.85 SMR = 0.93	0.40, 1.18 0.14, 1.30 0.24, 2.22 0.34, 1.75 0.34, 2.03	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	2 vs. 1 2 vs. 2.1 1 vs. 0	RR = 2.7 Obs. vs. exp. = 0.95 RR = NR	0.1, > 100 NR NR	Respiratory system	–	–	–	–	–	–	–	–	–	–	–	–
Bronchus, trachea, and lung	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	15 4 4 7 6	SMR = 0.74 SMR = 0.52 SMR = 0.90 SMR = 0.88 SMR = 0.96	0.41, 1.22 0.14, 1.34 0.24, 2.29 0.35, 1.81 0.35, 2.09	–	–	–	–	Bronchus, trachea, and lung	–	–	–	–	–	–	–	–	–	–	–	–
Breast	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	2 2 0 0 0	SMR = 1.57 SMR = 5.11 NR NR NR	0.19, 5.66 0.62, 18.45 NR NR NR	–	–	–	–	Breast	–	–	–	–	–	–	–	–	–	–	–	–
Prostate	–	–	–	–	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	5 vs. 1 5 vs. 3.1 4 vs. 1	RR = 7.7 Obs. vs. exp. = 1.6 RR = 8.2	0.9, > 100 NR 0.8, > 100	Prostate	–	–	–	–	Never exposed Ever low or high ≥ 1 year low or high > 1 year high	10 19 16 9	OR = 1.00 OR = 1.34 OR = 1.36 OR = 1.08	Referent 0.62, 2.91 0.61, 3.02 0.44, 2.69	PFOS quartile 1 PFOS quartile 2 PFOS quartile 3 PFOS quartile 4 Per 10 ng/mL plasma PFOS	179 178 180 176 713	RR = 1.00 RR = 1.35 RR = 1.31 RR = 1.38 RR = 1.05	Referent 0.97, 1.87 0.94, 1.82 0.99, 1.93 0.97, 1.14
Urinary organs	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	3 0 0 3 3	SMR = 1.59 NR NR SMR = 4.02 SMR = 5.11	0.33, 4.65 NR NR 0.83, 11.75 1.05, 14.93	–	–	–	–	Urinary organs	–	–	–	–	–	–	–	–	–	–	–	–
Bladder (with or without other urinary)	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	3 0 0 3 3	SMR = 4.81 NR NR SMR = 12.77 SMR = 16.12	0.99, 14.06 NR NR 2.63, 37.35 3.32, 47.14	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	0 vs. 1 0 vs. 1.0 0 vs. 0	RR = NR Obs. vs. exp. = 0 RR = NR	NR NR NR	Bladder (with or without other urinary)	Never exposed Ever low Ever low or high Ever high ≥ 1 year high or low ≥ 1 year high 0< 1 year high 1< 5 years high 5< 10 years high ≥ 10 years high	2 7 9 6 6 3 2 4 3 2	SIR = 0.61 SIR = 2.26 SIR = 1.70 SIR = 1.74 SIR = 1.31 SIR = 1.12 SIR = 1.07 RR = 1.00 SIR = 0.95 RR = 0.83 SIR = 2.72 RR = 1.92 SIR = 1.43 RR = 1.52	0.07, 2.19 0.91, 4.67 0.77, 3.22 0.64, 3.79 0.48, 2.85 0.23, 3.27 0.12, 3.85 Referent 0.25, 2.43 0.15, 4.65 0.55, 73.95 0.30, 12.06 0.16, 5.15 0.21, 10.99	–	–	–	–	PFOS quartile 1 PFOS quartile 2 PFOS quartile 3 PFOS quartile 4 Per 10 ng/mL plasma PFOS	83 84 83 82 332	RR = 1.00 RR = 0.76 RR = 0.93 RR = 0.70 RR = 0.93	Referent 0.50, 1.16 0.61, 1.41 0.46, 1.07 0.83, 1.03
Bladder, continued	Total cohort 0< 1 year high 1< 5 years high 5< 10 years high ≥ 5 years high ≥ 10 years high [Sensitivity analysis accounting for underascertainment]	1.93* 0.52* 0.80* 0.30* 0.61* 0.31*	SIR = 1.41 SIR = 1.27 SIR = 1.11 SIR = 2.57 SIR = 2.00 SIR = 1.53	0.79, 2.33 0.26, 3.69 0.39, 2.49 0.63, 6.89 0.75, 4.29 0.26, 4.78	–	–	–	–	–	–	–	–
Malignant melanoma	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	3 1 0 2 1	SMR = 1.67 SMR = 1.38 NR SMR = 2.62 SMR = 1.67	0.34, 4.88 0.03, 7.67 NR 0.32, 9.46 0.04, 9.25	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	5 vs. 0 5 vs. 2.2 3 vs. 0	RR = 12 Obs. vs. exp. = 2.3 RR = 10	1.0, > 100 NR 0.7, > 100	Malignant melanoma	–	–	–	–	Never exposed Ever low or high ≥ 1 year low or high > 1 year high	4 7 5 4	OR = 1.00 OR = 1.08 OR = 0.90 OR = 1.01	Referent 0.31, 3.72 0.24, 3.43 0.25, 4.11	–	–	–	–
Thyroid	–	–	–	–	Chemical vs. film Chemical observed vs. expected Long-term, high-exposure chemical vs. long-term film	1 vs. 0 1 vs. 1.0 0 vs. 0	RR = NR Obs. vs. exp. = 1 RR = NR	NR NR NR	Thyroid	–	–	–	–	–	–	–	–	–	–	–	–
Lymphatic and hematopoietic	Total cohort Non-exposed only Ever low, never high Ever high ≥ 1 year high	4 3 0 1 1	SMR = 0.70 SMR = 1.37 NR SMR = 0.43 SMR = 0.56	0.19, 1.80 0.28, 4.00 NR 0.01, 2.40 0.01, 3.08	–	–	–	–	Lymphatic and hematopoietic	–	–	–	–	–	–	–	–	–	–	–	–
All sites	PFOS in serum (ng/mL): - Mean, male cases - Mean, female cases - Median, male cases - Median, female cases - Range, male cases - Range, female cases - Mean, Athens males - Mean, Athens females - Median, Athens males - Median, Athens females - Range, Athens males - Range, Athens females - Mean, Argolida males - Mean, Argolida females - Median, Argolida males - Median, Argolida females - Range, Argolida males - Range, Argolida females	Cases: 17 males, 23 females Athens controls: 27 males, 29 females Argolida controls: 27 males, 59 females	[No RRs] 12.97 8.18 11.33 8.00 4.98–26.38 2.12–25.70 14.93 7.49 13.69 7.03 6.97–30.36 2.27–16.63 13.63 9.28 10.47 8.47 3.46–40.36 2.63–26.36	Analysis of variance P > 0.05	–	–	–	–	All sites	–	–	–	–	–	–	–	–	–	–	–	–
Digestive organs and peritoneum	–	–	–	–	–	–	–	–	Digestive organs and peritoneum	–	–	–	–	–	–	–	–	–	–	–	–
Esophagus	–	–	–	–	–	–	–	–	Esophagus	–	–	–	–	–	–	–	–	–	–	–	–
Colorectum	–	–	–	–	–	–	–	–	Colorectum	–	–	–	–	–	–	–	–	Quartile 1 (0.25–13.5 ng/mL PFOS) Quartile 2 (13.6–20.1 ng/mL PFOS) Quartile 3 (20.2–29.1 ng/mL PFOS) Quartile 4 (≥ 29.2 ng/mL PFOS) Per ng/mL PFOS Residents since ≤ 1995, cases diagnosed ≥ 2000 Quartile 1 Quartile 2 Quartile 3 Quartile 4	79 39 42 48 42 12 7 10	OR = 1.00 OR = 0.38 OR = 0.27 OR = 0.24 P-trend < 0.00001 OR = 0.96 OR = 1.00 OR = 0.19 OR = 0.13 OR = 0.12 P-trend < 0.00001	Referent 0.25, 0.59 0.17, 0.42 0.16, 0.37 0.95, 0.97 Referent 0.09, 0.38 0.06, 0.27 0.06, 0.23
Colon	–	–	–	–	–	–	–	–	Colon	–	–	–	–	–	–	–	–	–	–	–	–
Rectum	–	–	–	–	–	–	–	–	Rectum	–	–	–	–	–	–	–	–	–	–	–	–
Liver (with or without bile ducts)	–	–	–	–	–	–	–	–	Liver (with or without bile ducts)	PFOS in serum (ng/mL): - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC PFOS in liver (ng/g) - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC Ratio of PFOS in liver vs. paired serum - Mean ± SD, HCC - Median, HCC - Range, HCC - Mean ± SD, HCV+ HCC - Median, HCV+ HCC - Range, HCV+ HCC	HCC without HCV: 24 serum, 12 liver tissue, 11 paired HCC with HCV: 13 serum, 14 liver tissue, 12 paired	[No RRs] 13.3 ± 8.83 11.5 4.36–48.4 13.2 ± 6.52 11.4 4.04–26.4 6.24 ± 3.89 4.96 1.92–13.7 8.2 ± 11.3 4.12 2.28–42.5 0.67 ± 0.53 0.49 0.10–1.86 0.64 ± 0.88 0.35 0.15–3.37	Kruskal-Wallis rank test for group difference in liver-to-serum ratio: P > 0.05	–	–	–	–	–	–	–	–
									Liver, continued	PFOS in serum (ng/mL): - Mean ± SD, HCV - Median, HCV - Range, HCV - Mean ± SD, normal - Median, normal - Range, normal PFOS in liver (ng/g) - Mean ± SD, HCV - Median, HCV - Range, HCV - Mean ± SD, normal - Median, normal - Range, normal Ratio of PFOS in liver vs. paired serum - Mean ± SD, HCV - Median, HCV - Range, HCV	HCV cirrhosis: 38 serum, 38 liver tissue, 32 paired Normal: 25 serum, 9 liver tissue, 0 paired	[No RRs] 16.6 ± 19.0 13.7 1.12–126 8.48 ± 6.62 7.29 1.43–34.9 5.03 ± 3.37 2.35 0.375–12.5 5.22 ± 2.81 5.03 1.30–10.8 0.40 ± 0.24 0.33 0.04–1.27	Kruskal-Wallis rank test for group difference in liver-to-serum ratio: P > 0.05	–	–	–	–	–	–	–	–
Pancreas	–	–	–	–	–	–	–	–	Pancreas	–	–	–	–	–	–	–	–	–	–	–	–
Respiratory system	–	–	–	–	–	–	–	–	Respiratory system	–	–	–	–	–	–	–	–	–	–	–	–
Bronchus, trachea, and lung	–	–	–	–	–	–	–	–	Bronchus, trachea, and lung	–	–	–	–	–	–	–	–	–	–	–	–
Breast	–	–	–	–	Per ng/mL of serum PFOS	31 cases and 98 controls with PFOS 9 cases and 69 controls with PFOS and covariates	OR = 1.01 (unadjusted, all subjects) OR = 1.01 (unadjusted, subjects with covariate data) OR = 1.03 (adjusted)	1.003, 1.02 (unadjusted, all subjects) 0.99, 1.03 (unadjusted, subjects with covariate data) 1.001, 1.07 (adjusted)	Breast	–	–	–	–	–	–	–	–	–	–	–	–
Prostate	–	–	–	–	–	–	–	–	Prostate	–	–		–	PFOS ≤ 8.3 ng/mL (control median) PFOS > 8.3 ng/mL PFOS > 8.3 ng/mL, Gleason score 2–6 PFOS > 8.3 ng/mL, Gleason score 2–7 PFOS > 8.3 ng/mL, PSA ≤ 10 ng/mL PFOS > 8.3 ng/mL, PSA ≥ 11 ng/mL PFOS ≤ 8.3 ng/mL, no family history PFOS > 8.3 ng/mL, no family history PFOS ≤ 8.3 ng/mL, family history PFOS > 8.3 ng/mL, family history	92 109 35 70 65 44 72 20 89 20	OR = 1.0 OR = 1.0 OR = 0.7 OR = 1.1 OR = 1.2 OR = 0.8 OR = 1.0 OR = 1.2 OR = 0.9 OR = 2.7	Referent 0.6, 1.5 0.4, 1.3 0.7, 1.9 0.7, 2.0 0.4, 1.3 Referent 0.6, 2.5 0.5, 1.4 1.04, 6.8	–	–	–	–
Urinary organs	–	–	–	–	–	–	–	–	Urinary organs	–	–	–	–	–	–	–	–	–	–	–	–
Malignant melanoma	–	–	–	–	–	–	–	–	Malignant melanoma	–	–	–	–	–	–	–	–	–	–	–	–
Thyroid	–	–	–	–	–	–	–	–	Thyroid	–	–	–	–	–	–	–	–	–	–	–	–
Lymphatic and hematopoietic	–	–	–	–	–	–	–	–	Lymphatic and hematopoietic	–	–	–	–	–	–	–	–	–	–	–	–

*Expected additional bladder cases among 495 eligible nonrespondents based on doubling of US bladder cancer rates

Abbreviations: CI: confidence interval; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; NR: not reported; OR: odds ratio; PFOS: perfluorooctanesulfonate; PSA: prostate-specific antigen; RR: rate ratio or relative risk; SD: standard deviation; SIR: standardized incidence ratio; SMR: standardized mortality ratio.

Figure 1. Median (or geometric mean) serum levels of perfluorooctanoic acid (PFOA) measured in directly, intermittently, and indirectly (background) exposed workers (Parkersburg, West Virginia; Cottage Grove, Minnesota; Decatur, Alabama; and Antwerp, Belgium) and in community members in Parkersburg and elsewhere in the United States. PTFE: polytetrafluoroethylene.

Figure 2. Median (or geometric mean) serum levels of perfluorooctanesulfonic acid (PFOS) measured in directly and indirectly (background) exposed workers (Decatur, Alabama; Cottage Grove, Minnesota; and Antwerp, Belgium) and in community members in Parkersburg, West Virginia, and elsewhere in the United States.

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