Toxic Metals and Their Emerging Role as Risk Factors in Hormone-Related Reproductive Cancers

Industrialization has led to global environmental pollution, exposing individuals to toxic metals (such as cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr)) on a daily basis. Lifelong exposure to toxic metals, even at low levels, endangers human health due to their accumulation and long biological half-lives. Additionally, some of these metals are classified as proven or probable human carcinogens according to the International Agency for Research on Cancer (IARC) (Group 1: Cd, As, Ni, Cr; Group 2A: Pb) and/or exhibit hormone-like properties, classifying them as metallohormones. Given the growing evidence linking these substances to reproductive cancers, this review summarizes human studies on toxic metal exposure and hormone-dependent cancers, focusing on breast, prostate, testicular, ovarian, and uterine cancers. Specific metals were included in our review due to their classification as proven or probable carcinogens (As, Cd, Ni, Cr, Pb), and their listing by WHO as chemicals of major public health concern (As, Cd, Pb, Hg). Variations in study results are largely driven by cancer type, studied metal, individual differences, and geography. Breast and prostate cancers, being common and well-studied, show strong links to Cd and As, potential associations with Pb, and mixed evidence for Hg, Ni, and Cr depending on sample type and study design. However, important knowledge gaps remain, particularly regarding the effects of combined metal exposures, the assessment of metal levels in tumor tissues, and the limited evidence available for less-studied cancers such as ovarian and testicular cancer.