Phthalate Exposure, Metabolism Capability, and Breast Cancer Risk: Case-Control Analysis Nested in a Large-Scale Long-Term Follow-Up Cohort

Abstract

Background : Phthalates are widely used in a variety of products from plastics to personal-care items. Their estrogenic activity may increase breast cancer risk, but the causality in humans was rarely assessed by longitudinal cohort studies. Method: This case-control study nested in a large-scale long-term follow-up cohort. A total of 119 newly developed cases of breast cancer and 245 matched controls were selected from a community-based cohort of 11,923 female participants, who were enrolled in 1991-1992 and followed to 2010 in Taiwan. Eleven metabolites of seven phthalates in urine samples collected at entry and follow-up examinations were measured using liquid chromatography/electrospray ionization tandem mass spectrometry. The DEHP metabolism capability was evaluated by the percentages of specific metabolite in total DEHP metabolites. Finding : Elevated urinary concentrations of total DEHP metabolites (>0·38 μmol/g creatinine) combined with elevated percentages of MEHP in total DEHP metabolites level (MEHP% >6·7%) had an increased odds ratio (OR) of breast cancer (OR= 2·68, 95% confidence interval, 1·47-4·89) after adjustment for age at menarche. There were no significant associations between the breast cancer risk and the baseline urinary concentrations of MEP, MMP, MiBP, MnBP, and MBzP, while MiNP was not detected in all urine samples. Analysis of 115 pairs of urine samples collected at study entry and follow-up visit showed higher correlation coefficients for the percentage of specific DEHP metabolite in total DEHP metabolites than for the urinary concentration of specific DEHP metabolites. Interpretation: The findings suggest that high DEHP exposure and high MEHP percentage may increase the risk of breast cancer, and DEHP metabolism capability is more stable than DEHP exposure over time. Funding Statement: Supported by grants (EH-102-SP-01 and EH-103-SP-01) from National Health Research Institutes, Ministry of Health and Welfare, as well as grant (MOST 103-2314-B-001-005-MY3) from the Ministry of Science and Technology, Executive Yuan, Taipei, Taiwan. Declaration of Interests: We declare that we have no conflict of interest and none of the funding organization played a role in the design and conducted of this study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript. Ethics Approval Statement: This study was approved by the Institutional Review Board of the National Taiwan University College of Public Health and by the National Health Research Institutes (NHRI).