Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and have been detected in human blood. Although PFAS may increase the risk of breast cancer in humans, findings from previous epidemiological studies on the link between PFAS and breast cancer are...

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Main Authors: Hiroaki Itoh, Kouji H. Harada, Gerson Shigeaki Hamada, Zhaoqing Lyu, Tomoko Fujitani, Mariko Harada Sassa, Taiki Yamaji, Shoichiro Tsugane, Motoki Iwasaki
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Environmental Health
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Online Access:https://doi.org/10.1186/s12940-025-01168-5
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author Hiroaki Itoh
Kouji H. Harada
Gerson Shigeaki Hamada
Zhaoqing Lyu
Tomoko Fujitani
Mariko Harada Sassa
Taiki Yamaji
Shoichiro Tsugane
Motoki Iwasaki
author_facet Hiroaki Itoh
Kouji H. Harada
Gerson Shigeaki Hamada
Zhaoqing Lyu
Tomoko Fujitani
Mariko Harada Sassa
Taiki Yamaji
Shoichiro Tsugane
Motoki Iwasaki
author_sort Hiroaki Itoh
collection DOAJ
description Abstract Background Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and have been detected in human blood. Although PFAS may increase the risk of breast cancer in humans, findings from previous epidemiological studies on the link between PFAS and breast cancer are controversial. Additionally, most studies of PFAS to date did not distinguish between isomers. Here, we examined the association of PFAS exposure and breast cancer risk in Brazilian women, who represent a racially and ethnically diverse group. Methods We conducted a case-control study of 471 women with breast cancer and 471 matched controls attending hospitals in São Paulo, Brazil from 2001 to 2006. Plasma concentrations of PFAS congeners were measured using in-port arylation gas chromatography–isotope dilution mass spectrometry with electron capture negative ionization. Linear and branched PFAS isomers were isolated and quantified separately. We derived multivariable-adjusted odds ratios and 95% confidence intervals for breast cancer and hormone-receptor subtypes according to plasma PFAS concentration. Results In overall analyses, higher plasma concentrations of n-perfluoroheptane sulfonate (n-PFHpS), perfluoro-3-methyl-heptane sulfonate (3 m-PFOS), and n-perfluorononanoic acid were significantly associated with increased risk of breast cancer. Adjusted odds ratios for low, medium, and high n-PFHpS concentrations were 1.00, 1.28, and 2.00 (95% confidence interval = 1.15, 3.48), respectively (P for trend = 0.015). Furthermore, plasma 3 m-PFOS concentration and total perfluorooctanoic acid concentration were significantly associated with increased risk of breast cancer among mixed-ethnicity women. In Caucasian women, a higher plasma perfluoro-4-methyl-heptane sulfonate concentration was also associated with increased risk of breast cancer. Increased plasma n-PFHpS concentration was significantly associated with higher risk of hormone receptor-positive breast cancer but not with increased risk of hormone receptor-negative breast cancer. Conclusions Several plasma PFAS appear to increase the risk of breast cancer. Our findings suggest the importance of isomer analysis, subgroup analysis by ethnicity, and breast cancer subtype analysis for accurately characterizing this risk. Clinical trial number Not applicable.
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spelling doaj-art-9e8a840855cd41279f2b8eafa5a9bb822025-08-20T02:10:17ZengBMCEnvironmental Health1476-069X2025-03-0124111410.1186/s12940-025-01168-5Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control studyHiroaki Itoh0Kouji H. Harada1Gerson Shigeaki Hamada2Zhaoqing Lyu3Tomoko Fujitani4Mariko Harada Sassa5Taiki Yamaji6Shoichiro Tsugane7Motoki Iwasaki8Department of Epidemiology and Environmental Health, Juntendo University Faculty of MedicineDepartment of Health and Environmental Sciences, Kyoto University Graduate School of MedicineNikkei Disease Prevention CenterDepartment of Health and Environmental Sciences, Kyoto University Graduate School of MedicineDepartment of Health and Environmental Sciences, Kyoto University Graduate School of MedicineDepartment of Health and Environmental Sciences, Kyoto University Graduate School of MedicineDivision of Epidemiology, National Cancer Center Institute for Cancer ControlDepartment of Epidemiology and Social Medicine, International University of Health and Welfare Graduate School of Public HealthDivision of Epidemiology, National Cancer Center Institute for Cancer ControlAbstract Background Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and have been detected in human blood. Although PFAS may increase the risk of breast cancer in humans, findings from previous epidemiological studies on the link between PFAS and breast cancer are controversial. Additionally, most studies of PFAS to date did not distinguish between isomers. Here, we examined the association of PFAS exposure and breast cancer risk in Brazilian women, who represent a racially and ethnically diverse group. Methods We conducted a case-control study of 471 women with breast cancer and 471 matched controls attending hospitals in São Paulo, Brazil from 2001 to 2006. Plasma concentrations of PFAS congeners were measured using in-port arylation gas chromatography–isotope dilution mass spectrometry with electron capture negative ionization. Linear and branched PFAS isomers were isolated and quantified separately. We derived multivariable-adjusted odds ratios and 95% confidence intervals for breast cancer and hormone-receptor subtypes according to plasma PFAS concentration. Results In overall analyses, higher plasma concentrations of n-perfluoroheptane sulfonate (n-PFHpS), perfluoro-3-methyl-heptane sulfonate (3 m-PFOS), and n-perfluorononanoic acid were significantly associated with increased risk of breast cancer. Adjusted odds ratios for low, medium, and high n-PFHpS concentrations were 1.00, 1.28, and 2.00 (95% confidence interval = 1.15, 3.48), respectively (P for trend = 0.015). Furthermore, plasma 3 m-PFOS concentration and total perfluorooctanoic acid concentration were significantly associated with increased risk of breast cancer among mixed-ethnicity women. In Caucasian women, a higher plasma perfluoro-4-methyl-heptane sulfonate concentration was also associated with increased risk of breast cancer. Increased plasma n-PFHpS concentration was significantly associated with higher risk of hormone receptor-positive breast cancer but not with increased risk of hormone receptor-negative breast cancer. Conclusions Several plasma PFAS appear to increase the risk of breast cancer. Our findings suggest the importance of isomer analysis, subgroup analysis by ethnicity, and breast cancer subtype analysis for accurately characterizing this risk. Clinical trial number Not applicable.https://doi.org/10.1186/s12940-025-01168-5Per- and polyfluoroalkyl substancesBreast cancerSouthern hemisphereMultiethnic
spellingShingle Hiroaki Itoh
Kouji H. Harada
Gerson Shigeaki Hamada
Zhaoqing Lyu
Tomoko Fujitani
Mariko Harada Sassa
Taiki Yamaji
Shoichiro Tsugane
Motoki Iwasaki
Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
Environmental Health
Per- and polyfluoroalkyl substances
Breast cancer
Southern hemisphere
Multiethnic
title Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
title_full Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
title_fullStr Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
title_full_unstemmed Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
title_short Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case–control study
title_sort plasma perfluoroalkyl substances and breast cancer risk in brazilian women a case control study
topic Per- and polyfluoroalkyl substances
Breast cancer
Southern hemisphere
Multiethnic
url https://doi.org/10.1186/s12940-025-01168-5
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