In utero exposure to poly− and perfluoroalkyl substances (PFASs) and subsequent breast cancer

Cohn, Barbara A.; Merrill, Michele A. La; Krigbaum, Nickilou Y.; Wang, Miaomiao; Park, June Soo; Petreas, Myrto; Yeh, Gregory; Hovey, Russell C.; Zimmermann, Lauren; Cirillo, Piera M.

doi:10.1016/j.reprotox.2019.06.012

Cited by 31 publications

(11 citation statements)

References 57 publications

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“…This possibility is corroborated by the findings of different effects of o,p'-DDT, p,p'-DDT and p,p'-DDE on multiple reproductive health outcomes [25][26][27][28][29]. Moreover, PFOS and EtFOSAA were differentially associated with daughter's breast cancer risk in the CHDS [14]. To test this hypothesis, we assessed the metabolite profiles associated with serum EtFOSAA levels, PFOS levels and the ratio of EtFOSAA to PFOS (as an indicator of active exposure) in the CHDS F0 generation, and compared the similarity and difference of metabolic pathways.…”

Section: Introductionmentioning

confidence: 63%

“…We found that high EtFOSAA exposure combined with high maternal cholesterol predicted a 3.6-fold increased risk of breast cancer in daughters. Conversely, maternal PFOS was associated with decreased breast cancer risk in daughters [14]. Although the underlying mechanisms are not well understood, the link between maternal endocrine disruptor exposure and offspring breast cancer risks is mostly established in mammary gland development of the offspring [10,11,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum

Cirillo

et al. 2019

Reproductive Toxicology

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High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk.

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Section: Introductionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum

Cirillo

et al. 2019

Reproductive Toxicology

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“…In another nested case-control design, Cohn et al (2019) examined the association between pregnancy concentration of PFAS with breast cancer risk in the female offspring after 54 years of follow-up. Out of 9,300 daughters born in 1959 to 167 archived maternal samples drawn during pregnancy whose daughters had been diagnosed (cases: n = 102) and matched controls (n = 310) were selected.…”

Section: J8 Carcinogenicity Outcomesmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

311

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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“…For example, exposure to environmental chemicals during pregnancy-such as DDT, polychlorinated biphenyls, and polyfluoroalkyl and PFAS-alter breast cancer risk in perimenopausal female offspring. 33,34,37,38 Diethylstilbestrol (DES), a drug prescribed for women from 1938 to 1971 to prevent miscarriage, exemplifies how pregnancy is a susceptible time period for breast development in women and their daughters. One in six (vs. one in eight in the general population) DES-prescribed pregnant women developed breast cancer (relative risk = 1.27, 95% confidence interval [CI] = 1.07-1.52), 85 and a higher breast cancer risk in DES daughters over 40 years of age also is reported (hazard ratio = 1.82, 95% CI = 1.04-3.18), 86 among numerous other adverse health outcomes.…”

Section: Breast Development and Healthmentioning

confidence: 99%

Environmental Factors Involved in Maternal Morbidity and Mortality

Boyles

Beverly

Fenton

et al. 2021

Journal of Women's Health

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Nongenetic, environmental factors contribute to maternal morbidity and mortality through chemical exposures via air, water, soil, food, and consumer products. Pregnancy represents a particularly sensitive window of susceptibility during which physiological changes to every major organ system increase sensitivity to chemicals that can impact a woman's long-term health. Nonchemical stressors, such as low socioeconomic status, may exacerbate the effects of chemical exposures on maternal health. Racial/ethnic minorities are exposed disproportionately to both chemicals and nonchemical stressors, which likely contribute to the observed health disparities for maternal morbidities and mortality. Epidemiological studies linking exposures to adverse maternal health outcomes underscore the importance of environmental health impacts, and mechanistic studies in model systems reveal how chemicals perturb biological pathways and processes. Environmental stressors are associated with a variety of immediate maternal health impacts, including hypertensive disorders of pregnancy, fibroids, and infertility, as well as long-term maternal health impacts, such as higher risk of breast cancer and metabolic disorders. Identifying and reducing a pregnant woman's environmental exposures is not only beneficial to her offspring but also important to preserve her short-and long-term health.

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In utero exposure to poly− and perfluoroalkyl substances (PFASs) and subsequent breast cancer

Cited by 31 publications

References 57 publications

Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum

Metabolome Wide Association Study of Serum Poly and Perfluoroalkyl Substances (PFASs) in Pregnancy and Early Postpartum

Risk to human health related to the presence of perfluoroalkyl substances in food

Environmental Factors Involved in Maternal Morbidity and Mortality

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