Elevated phthalate exposure and metabolic susceptibility increased breast cancer risk: A 20-y follow-up study in Taiwan.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
123
Journal Issue
11
Start Page
Article number e2507008123
ISSN
1091-6490
Date Issued
2026-03-17
Author(s)
Chen, Hui-Chi
You, San-Lin
Sun, Chien-Wen
Yang, Hwai-I
Chiang, Chun-Ju
Wang, Li-Yu
Sun, Chien-An
Liu, Jessica
Jen, Chin-Lan
Chen, Yuh-An
Wang, Shu-Li
Lu, Yen-Shen
Hsiung, Chao A
Chen, Chien-Jen
Abstract
Widely used phthalates, especially di-(2-ethylhexyl) phthalate (DEHP), increase breast cancer risk in experimental animals and humans, but long-term follow-up evidence of its human breast carcinogenicity remains inconclusive. This nested case-control study included 119 invasive breast cancer cases and 245 matched controls from a longitudinal cohort of 11,923 women recruited in 1991-1992 and followed to 2010 in Taiwan. Urine samples at baseline and follow-up visit were tested for 11 metabolites of seven phthalates using LC-ESI-MS/MS. DEHP metabolism susceptibility was evaluated by the percentage of mono-2-ethylhexyl phthalate (MEHP%) in the sum of five DEHP metabolites (∑DEHP). Odds ratios (ORs) with 95% CI from conditional logistic regression were used to examine risk predictors. DEHP was the only phthalate significantly associated with breast cancer risk. Risk increased significantly with elevated urinary levels of ∑DEHP (> 0.381 μmol/g creatinine, OR = 1.71, 95% CI = 1.02 to 2.43), MEHP (> 0.022 μmol/g creatinine, OR = 1.87, 95% CI = 1.07 to 3.25), and MEHP% (> 6.7%, OR = 1.65, 95% CI = 0.96 to 2.82). Elevated ∑DEHP and MEHP% combined with early menarche (≤ 14 years) was associated with further increased risk (OR = 7.52, 95% CI = 2.68 to 21.05). The intraclass correlation coefficient between paired baseline and follow-up samples of 152 women was 0.06 for ∑DEHP and 0.31 for MEHP%. High DEHP exposure, high MEHP%, and early menarche were associated with increased breast cancer risk. MEHP% was a better biomarker for DEHP metabolism.
Subjects
DEHP
MEHP%
breast cancer
follow-up study
metabolic susceptibility
Type
text::journal::journal article