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Comparable episodes of care were observed for most diseases between PFOS-exposed and non-exposed workers, notable associations for malignancies [RREpC (95% CI)] included: colon cancer (n=4 among exposed workers) 5.4 (0.5->100), prostate cancer (n=5 among exposed workers) 7.7 (0.9->100) and melanoma (n=5 among exposed workers) 12 (1.0->100). We then reviewed the evidence from the identified studies, in groups by overall study design, with consideration of study design features to summarize the strength of the evidence regarding the links between PFAS and cancer and to identify study design features that would be most likely to yield informative results in future studies. -Full time employees who retired were eligible for care after retirement and were included in the study. Vieira VM, Hoffman K, Shin HM, Weinberg JM, Webster TF, Fletcher T. Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis, Bias magnification in ecologic studies: a methodological investigation, Trade-offs of Personal Versus More Proxy Exposure Measures in Environmental Epidemiology. 2013), which is a limitation. However, evidence is limited and not entirely consistent. To determine the impact of PFAS exposure on prostate cancer cells, we performed a cell viability assay using a benign human prostate cell line, RWPE-1, and a derivative cancerous cell line, RWPE-kRAS. The occupational studies, whether focused on PFOS (3M plant in Alabama) or PFOA (Dupont plant in West Virginia, 3M plant in Minnesota, and plant in Veneto, Italy), do not show a consistent pattern of elevation of the incidence of cancer at any specific site. The full text of the final search terms is included in the supplemental material. -Compared PFAS contaminated areas with uncontaminated areas, but did not do analyses by PFAS level or specific PFAS type. No other control for confounding. Discussion: Each study's design has strengths and limitations. ORs (95% CI) for 2. Bethesda, MD 20894, Web Policies EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), Schrenk D, Bignami M, Bodin L, Chipman JK, del Mazo J, Grasl-Kraupp B, Hogstrand C, et al. There have been 16 cohort or case-cohort studies, primarily focused on PFOA or PFOS (Table 1); 11 of which considered 3 U.S. (or primarily U.S.) occupational cohorts with high exposures (PFOA: median serum concentrations in various groups of exposed workers 1135200 ng/ml, maximum concentration reported 92,030 ng/ml; PFOS: geometric mean concentrations for workers at plant using PFOS 941 ng/ml, maximum concentration reported 10,600 ng/ml) [Alexander et al., 2003; Olsen et al., 2004; Alexander and Olsen, 2007; Grice, et al., 2007; Leonard et al., 2008; Steenland and Woskie, 2012; Consonni et al., 2013 (primarily U.S. cohort); Steenland et al., 2015; Gilliland and Mandel, 1993; Lundin et al., 2009; Raleigh et al., 2014], and 1 of which was for an occupational cohort in Italy with high exposures (geometric mean serum concentrations: PFOA 4,048 ng/ml, PFOS 148.8 ng/ml; maximum concentrations reported: PFOA 91,900 ng/ml, PFOS 3,386 ng/ml) (Girardi and Merler, 2019) (Table 1). Retrospective follow-up study via survey of occupational cohort (medical records confirmation sought for self-reported cancers). Retrospective occupational cohort study via survey of occupational cohort (medical records confirmation sought for self-reported cancers) and death certificate matching. It should also be noted that there is some overlap of testicular cancer cases in these two studies (Barry et al. Another example is co-exposure to PFOA and tetrafluoroethylene (TFE) in the study by Consonni et al. Schwanz TG, Llorca M, Farr M, Barcel D. Perfluoroalkyl substances assessment in drinking waters from Brazil, France and Spain. Each study design has strengths and limitations which need to be carefully considered when interpreting study findings. Six (Hurley et al., 2018; Vassiliadou et al., 2010; Bonefelt-Jorgensen et al., 2011; Wielsoe et al.,2017; Hardell et al., 2014; Tsai et al., 2020) analyzed serum levels of PFAS at the time of, or after, diagnosis. However, the level of exposure to PFAS experienced by military personnel is unclear. Mancini FR, Cano-Sancho G, Gambaretti J, Marchand P, Boutron-Ruault MC, Severi G, Arveux P, Antignac JP, Kvaskoff M. Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort. Andersson EM, Scott K, Xu Y, Li Y, Olsson DS, Fletcher T, Jakobsson K. High exposure to perfluorinated compounds in drinking water and thyroid disease. Calculated odds ratios using logistic regression controlling for pregnancy history, oral contraceptive use, abortion, body mass index, education level, menopause, and stratified by age category (50 years and > 50 years). Similar comparisons were not possible for other cancer types. Overall, for the breast cancer studies, investigators generally found little or no association between disease and serum PFAS levels (estimated or measured). The second study was of a general population-based cohort exposed to background levels of PFOA and PFOS, with gender-specific median serum concentrations of 5.46.9 ng/ml (5th-95th percentile ranges 2.214.0) and 29.335.1 ng/ml (5th-95th percentile ranges 14.062.4) for PFOA and PFOS respectively (Eriksen et al, 2009). U.S. adults. The general-population study focused on PFOA had high exposure contrasts (measured serum PFOA concentrations in 20052006 in community cohort: median 24.2 ng/ml, range 0.254,752 ng/ml, also see Winquist et al., 2013) due to water contamination (Barry et al., 2013). Ingelido AM, Abballe A, Gemma S, Dellatte E, Iacovella N, De Angelis G, Zampaglioni F, Marra V, Miniero R, Valentini S, Russo F, Vazzoler M, Testai E, De Felip E. Biomonitoring of perfluorinated compounds in adults exposed to contaminated drinking water in the Vento Region, Italy. The authors present results from a model with linear terms for log. Kato K, Wong L-Y, Jia LT, Kuklenyik Z, Calafat AM. Our well-powered study found no association between serum PFAS and subsequent aggressive prostate cancer. Only the 3 types of cancer with a substantial number of cases were analyzed. at the National Cancer Institute, An official website of the United States government, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch. Firefighters, who have elevated PFOA levels from occupational exposure to firefighting foam, have an increased prostate cancer risk compared to the general population. 2013). The general population study with high exposure to PFOA resulting from drinking water contamination (Barry et al., 2013) found an excess of kidney and testicular cancer with increased estimated cumulative serum PFOA levels (although this excess was apparent only in the community population (87 cases), but not in the subset of workers (18 cases)). An official website of the United States government. Mastrantonio, et al. The study includes 400 cases of ALL (children <15 years) and 400 cases of thyroid cancer among the mothers, utilizing frequency matching and a shared control group. Other exposures, such as from diesel fumes, can come from vehicles at fire scenes and at fire stations. We included all primary epidemiologic studies that reported a quantitative estimate of association between at least one type of PFAS and at least one type of cancer. The only case-control study with high exposure contrasts was the one conducted by Vieira et al. Polymorphism in xenobiotic and estrogen metabolizing genes, exposure to perfluorinated compounds and subsequent breast cancer risk: A nested case-control study in the Danish National Birth Cohort, Mortality among employees of a perfluorooctanoic acid production plant, A mortality study on male subjects exposed to polyfluoroalkyl acids with high internal dose of perfluorooctanoic acid. 462 male employees at exposed plant, 1383 at unexposed workplace; follow-up during 19702018; Calculated SMRs relative to regional mortality rates, standardized by gender, 5-year age groups and 5-year calendar periods. (2013), Vieira et al. Calculated odds ratios using unconditional logistic regression, controlling for age at baseline, race/ethnicity, region of residence, date of blood draw, date of blood draw squared, season of blood draw, total smoking pack years, body mass index, family history of breast cancer, age at first full-term pregnancy, menopausal status at blood draw and pork consumption. Six of ten case-control studies measured PFAS serum levels after disease occurrence. In summarizing study findings, we noted the type of measure of association reported and summarized any notable effect estimates and their associated confidence intervals, including whether or not there was evidence of a dose-response relationship. Often many of these data sources may not be available. Tricco AC, Lillie E, Zarin W, OBrien KK, Colquhoun H, Levac D, et al. In our view there is also some, more limited, suggestive evidence for prostate cancer, but results are inconsistent. Freedman ND, Sampson JN, Silverman DT, Purdue, MP and Hofmann JN. Shin HM, Vieira VM, Ryan PB, Steenland K, Bartell SM. Thyroid. As a general problem in epidemiology, the time windows when PFAS exposure might be most likely to lead to cancer, if it does, are unknown. In 2016, at the age of 46, Marchetti was diagnosed with prostate cancer a diagnosis he alleges was caused by exposure to chemicals in turnout gear. Job history, categorized as no exposure, low potential exposure and high potential exposure (based on knowledge of major job-specific serum levels), some analyses also included a cumulative exposure measure that considered weighted years in each category, Workers with at least 1 year of cumulative employment at a manufacturing site producing PFOS (same site as, 1588 in analysis (included 188 who had died and 1400 who had not died and responded to the survey), follow up through 2002 (total of 11 bladder cancer cases), Calculated standardized incidence ratios (SIR) with the U.S. population (SEER data) as the reference population, standardized by age, gender and calendar period. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. We abstracted information about important study design features, types of PFAS studied, type of exposure assessment, PFAS serum concentrations in the cohort or study population (referring to referenced studies or other available studies when necessary), cancer types considered, study population characteristics and size, methods for control for confounding, and the main study findings. Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease. Arrieta-Cortes R, Farias P, Hoyo-Vadillo C, Kleiche-Dray M. Carcinogenic risk of emerging persistent organic pollutant perfluorooctane sulfonate (PFOS): a proposal of classification, Toxicological Profile for Perfluoroalkyls, Human exposure to perfluoroalkyl substances near a fluorochemical industrial park in China. Overview For more information, contact Dr. Rena Jones or Dr. Mary Ward. In 2017, the International Agency for Research on Cancer (IARC) classified perfluorooctanoic acid (PFOA), the most well-studied per- and polyfluoroalkyl substance (PFAS), as a possible human carcinogen based in part on limited epidemiologic evidence of associations with cancers of the kidney and testis in heavily exposed subjects. Studies have associated PFAS with harmful effects in laboratory animals. PFAS chemicals, which have turned up in drinking water in cities across the US, have been linked to non-Hodgkin's lymphoma and kidney, testicular, prostate, breast, liver, and ovarian cancers. On the other hand, low-exposure cohorts are more applicable to the exposures of most of the population, and if large enough, may also provide important evidence (e.g., Eriksen et al. The Working group initiates, coordinates, and provides guidance toDCEG research with emphasis on overcoming challenges to the research and initiating studies to address gaps in the science. For instance, the American Cancer Society notes that PFOA (perfluorooctanoic acid), which is a compound of PFAS, is linked to the development of other cancers in humans, such as: Testicular. The third general population study, focused on breast cancer and found a weak positive association with baseline serum PFOSA concentrations without a monotonic trend (Bonefeld-Jorgensen et al., 2014). Calculated odds ratios using conditional logistic regression (conditioned on matching factors), adjusted for total serum lipids, body mass index (continuous), smoking status, physical activity, education level, history of benign breast disease, family history of breast cancer, parity, age at first full-term pregnancy, breastfeeding duration, age at menarche, age at menopause, current use of menopausal hormone therapy, use of oral contraceptives, adherence to healthy and Western and Mediterranean diet patterns. PMC7946751 DOI: 10.1016/j.envres.2020.110690 Abstract Background: Many communities have had water contaminated by PFAS, and cancer is one of the important community concerns related to PFAS exposure. Part of the reason for concern about PFAS and cancer is that, in rats, administration of PFOA has been associated with development of testicular Leydig cell adenomas, pancreatic acinar cell adenomas, and hepatocellular adenomas or carcinomas, and with promotion of hepatocellular carcinoma development after treatment with N-nitrosodiethylamine (IARC, 2017); and PFOS administration has been associated with development of hepatocellular adenomas and thyroid follicular cell adenomas (Lau et al., 2007; Chang et al., 2014). WASHINGTON, DC - Congressman Brian Fitzpatrick (PA-01) and Congressman Brian Higgins (NY-26), co-chairs of the House Cancer Caucus, along with Congresswoman Kathy Castor (FL-14) introduced the Increasing Access to Lung Cancer Screening Act. In analyses relative to a regional worker population [SMRs (95% CIs) for quartiles 14 of estimated cumulative exposure]: -Cumulative serum levels estimated based on occupation and a large number of measured levels (, Compared plant workers to general population, also estimated time-varying cumulative exposure (in arbitrary relative unit-years based on occupational histories and a job-exposure matrix), PFOA serum concentrations or estimates were not provided (the main focus of the study was tetrafluoro-ethylene exposure), Workers in 6 plants (the largest of which was the Dupont plant in West Virginia, United States. Self-reported medical conditions in perfluorooctanesulfonyl fluoride manufacturing workers. For more information, contact Dr. Jonathan Hofmann. Health Deep Dives The Toxic Job of Being a Hero Could the high rates of cancer in firefighters be linked to the gear that's supposed to protect them? Retrospective cohort mortality study of workers in a polymer production plant including a reference population of regional workers, Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water. PFOS and EtFOSAA were included in same model (because PFOS is a metabolite of EtFOSAA). Overall, the evidence for an association between cancer and PFAS remains sparse. Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population, Time trends over 20032014 in the concentrations of selected perfluoroalkyl substances among US adults aged 20years: Interpretational issues. Dhingra R, Winquist A, Darrow LA, Klein M, Steenland K. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. There are also some suggestions in a few studies of an association with prostate cancer, but the data are inconsistent. Stephanie M. Lee BuzzFeed News Reporter Updated on March 4, 2020, 9:51 am Posted on March 3, 2020, 4:31 am Be one of the first to comment The incidence of thyroid cancer has been steadily increasing in recent decades in the United States and worldwide [].Although early or incidental detection of smaller tumors due to more advanced and frequent use of imaging technology may partially explain this increase [], research has highlighted the potential contribution of exposure to environmental pollutants to this . If controls are selected from people with other diseases (e.g., Vieira et al., 2013 and some controls in Wilsoe et al., 2017), measures of association can be biased downward if the control conditions (that are used for selection of the comparison group) are associated with exposure. Dangers Certain PFAS can accumulate and stay in the human body for long periods of time. In conditional logistic regression models ORs (95% CIs) comparing quartiles 24 to quartile 1 in single-pollutant models: PFOA 1.47 (0.772.80), 1.24 (0.642.41), 2.63 (1.335.20), trend p-value 0.007; Measured concentrations in serum collected from cancer patients (presumably after diagnosis), and from other patients at the time of a clinic visit.

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