Evidence-based identification of breast cancer and associated ovarian and uterus cancer risk components in source waters from high incidence area in the Pearl River Basin, China.

Breast cancer, ovarian cancer, and uterus cancer are among the most common female cancers. They are suspected to associate with exposures to specific environmental pollutants, which remain unidentified in source waters. In this work, we focused on the Pearl River Basin region in China, which experienced a high incidence of breast, ovarian, and uterus cancers. Combining cancer patient data, mammalian cell cytotoxicity analyses, and exhaustive historical and current chemical assessments, we for the first time identified source water components that promoted proliferation of mammalian cells, and confirmed their association with these female cancers via the estrogen receptor mediated pathway. Therefore, the components that have previously been found to enhance the proliferation of estrogen receptor-containing cells through endocrine disruption could be the crucial factor. Based on this, components that matched with this toxicological characteristic (i.e., estrogen-like effect) were further identified in source waters, including (1) organic components: phthalates, bisphenol A, nonylphenols, and per-/polyfluoroalkyls; (2) inorganic components: Sb, Co, As, and nitrate. Moreover, these identified water components were present at levels comparable to other regions with high female cancer prevalence, suggesting that the potential risk of these components may not be exclusive to the study region. Together, multiple levels of evidence suggested that long-term co-exposures to source water estrogenic components may be important to the development of breast, ovarian, and uterus cancers.