Association between phthalate exposure and risk of breast cancer in women: Based on NHANES 2015-2023
- VernacularTitle:邻苯二甲酸酯暴露与女性乳腺癌患病风险的关联：基于2015—2023年NHANES数据库
- Author:
Wenhua SHEN
1
;
Huijun XIE
1
;
Jian'an CHEN
1
Author Information
- Publication Type:Investigation
- Keywords: environmental exposure; phthalate; breast cancer; cross-sectional study; National Health and Nutrition Examination Survey
- From: Journal of Environmental and Occupational Medicine 2026;43(3):347-353
- CountryChina
- Language:Chinese
-
Abstract:
Background Breast cancer is one of the most common malignant tumors among women worldwide. The occurrence of breast cancer is related to multiple factors, including genetics, hormone levels, environmental pollution, and lifestyle. In recent years, more and more studies have begun to focus on the impact of environmental pollutants on breast cancer, but relevant research in China is still relatively limited. Objective To evaluate the association between phthalate exposure and the risk of breast cancer in adult women. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2015–2023. Participants were categorized into breast cancer cases and non-cancer controls based on Medical Conditions Questionnaire. Urine samples from included participants were analyzed using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to measure twelve phthalate metabolites: mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), monoisobutyl phthalate (MiBP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), etc. Logistic regression was used to investigate the association between phthalate exposure and breast cancer. Multiple comparisons were adjusted using the Bonferroni correction. Weighted quantile sum (WQS) regression was applied to assess the effects of mixed phthalate exposure. Sensitivity analyses were conducted including Bootstrap resampling, extreme value exclusion, and propensity score matching (PSM). Restricted cubic spline models were constructed to characterize potential dose-response relationships. Results A total of
1486 adult female participants were included, comprising 89 breast cancer cases. Levels of MECPP, MEHHP, MiBP, and MEOHP metabolites were significantly higher in the breast cancer cases compared to the controls (P<0.05). The logistic regression results showed that MECPP (OR=1.011, 95%CI: 1.002, 1.020) and MiBP (OR=1.020, 95%CI: 1.009, 1.030) were independent risk factors for breast cancer. After Bonferroni correction, the association between MiBP and breast cancer remained statistically significant (P<0.001). The WQS regression model adjusted for selected covariates showed that the combined phthalate exposure was associated with an increased breast cancer risk (OR=1.421, 95%CI: 1.183, 1.714, P<0.001). The mixed exposure analysis revealed that MiBP (weight=0.38), MECPP (weight=0.22), and MEOHP (weight=0.15) contributed 75% of the cumulative weight, highlighting their dominant influence on the association between phthalate mixtures and disease risk. The MiBP-breast cancer association remained robust across sensitivity analyses. Dose-response modeling indicated linear trends for both MECPP and MiBP (Pnonlinearity>0.05), with no evidence of non-linear associations. Conclusion High-level phthalate exposure is significantly associated with an increased risk of breast cancer in adult women. Among the metabolites studied, MiBP is identified as the most robust risk factor and MECPP also demonstrates a notable association. Furthermore, our findings suggest that phthalate mixtures may exert synergistic effects, collectively elevating breast cancer risk.
