Serum perfluoroalkyl substances and breast cancer risk in Japanese women: A case-control study

Sci Total Environ. 2021 Dec 15:800:149316. doi: 10.1016/j.scitotenv.2021.149316. Epub 2021 Jul 29.


Background: Perfluoroalkyl substances (PFASs) may contribute to causing breast cancer; however, associations between exposure to PFASs and risk of breast cancer are controversial.

Objectives: In the present study, we newly distinguished branched isomers of PFASs from their linear isomers and aimed to investigate the association between serum PFAS concentrations and breast cancer risk in Japanese women.

Methods: We used a case-control design to study 405 eligible matched pairs attending four hospitals in Nagano Prefecture, Japan from May 2001 to September 2005. We used in-port arylation gas-chromatography mass spectrometry with negative chemical ionization to measure serum concentrations of 20 PFAS congeners. We calculated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor subtypes by quartiles or tertiles of serum PFASs.

Results: After multivariable adjustment for breast cancer risk factors, we found that serum concentrations of 20 PFAS congeners were significantly inversely associated with risk of breast cancer. Comparing the extreme quartiles of linear isomers of perfluorooctane sulfonate or perfluorooctanoic acid, ORs were 0.15 (95% CI: 0.07, 0.33 P for trend <0.0001) and 0.21 95% CI: 0.10, 0.44 P for trend <0.0001). Among postmenopausal women, whereas we found the linear isomer of perfluorotridecanoic acid to be inversely associated with breast cancer risk, a medium degree of exposure to the branched isomer of perfluorotridecanoic acid was associated with a marginally increased risk of breast cancer (OR [95% CI] = 1.74 [0.98, 3.09]).

Discussion: In our case-control study, we found overall no association between serum PFAS concentrations and increased risk of breast cancer. Many inverse associations between serum PFAS concentrations and breast cancer risk were found.

Keywords: Congener; Epidemiology; Fluorinated chemical; Fluorochemical; Isomer; Perfluorochemical.

MeSH terms

  • Alkanesulfonic Acids*
  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / epidemiology
  • Case-Control Studies
  • Environmental Pollutants*
  • Female
  • Fluorocarbons*
  • Humans
  • Japan / epidemiology


  • Alkanesulfonic Acids
  • Environmental Pollutants
  • Fluorocarbons