Bisphenol A and cancer: a critical review of the epidemiologic literature with an emphasis on exposure assessment.

backgroundBisphenol A (BPA) is a high production volume chemical that has been used for decades in numerous consumer and industrial applications. Daily exposure to BPA is likely; it is readily detected in >90% of the general population despite being rapidly metabolized and excreted. BPA's toxicity, including endocrine disrupting activity, has sparked public health concern. We comprehensively reviewed the epidemiologic literature on the carcinogenicity of BPA and highlighted exposure assessment considerations that impact study interpretation.

methodsMultiple biomedical databases were searched through February 2025 for peer-reviewed cancer epidemiology studies that assessed associations with BPA exposure. Studies of the following designs (or a variant) were included: cohort, case-control, cross-sectional. A detailed bias assessment was conducted with guidance from the Report on Carcinogens Handbook and the International Agency for Research on Cancer Monographs Preamble.

resultsOf the 139 records identified, 43 epidemiological studies were reviewed; all were conducted in the general population. We focused the review on cancers of the breast and prostate because they had the highest number of cohort or case-control studies, but all cancer sites were summarized in the appendix for completeness. Generally, there were mixed results for associations with BPA. Interpretation was hampered by the high potential for exposure measurement error and the inability to characterize past BPA exposure, necessary to assess cancer outcomes with long latency. The majority of studies relied on biomonitoring using short-term biomarkers of recent BPA exposure, and measured BPA in urine at a single time point post-diagnosis; this failed to capture the critical time window of susceptibility, rule out reverse causation, or characterize temporal variation in BPA exposure.

conclusionsThe epidemiologic evidence was inadequate to evaluate the carcinogenicity of BPA - mainly due to exposure measurement error and misclassification, limited number of studies by cancer site, and heterogeneity in the results and study methodology. The inadequate evidence base cannot rule out potential carcinogenicity of BPA in humans. Future studies conducted within highly exposed occupational cohorts, with prospective and longitudinal collection of quantitative exposure data (e.g., BPA levels) and assessment of cancer outcomes or acute endpoints involved in established mechanisms of carcinogenesis (e.g., receptor mediated effects) are likely to be informative.