Abstract
Ovarian cancer research increasingly emphasizes the role of genetic factors, particularly estrogen, a key hormone also implicated in breast cancer. Hypotheses such as incessant ovulation and hormonal stimulation of ovarian epithelial cells support a hormonal etiology for ovarian cancer. This systematic review and meta-analysis evaluated the association between estrogen-related gene polymorphisms and ovarian cancer susceptibility. A comprehensive search was conducted in EMBASE, LILACS, PubMed, Scopus, Web of Science, and Google Scholar. Study selection, data extraction, and risk of bias assessment were performed independently by five reviewers. We included observational studies in humans, with no restrictions on language or publication date that investigated associations between estrogen-related gene polymorphisms and ovarian cancer occurrence or susceptibility. Exclusion criteria included studies not addressing the research question, those involving non-human subjects, secondary analyses, and genes unrelated to estrogen. Thirty studies met inclusion criteria. Meta-analysis showed that the A allele of rs4680 in the COMT gene (OR 0.85; 95% CI: 0.73-0.99; P = 0.0373) and the G allele of rs1695 in GSTP1 (OR 0.69; 95% CI: 0.51-0.92; P = 0.012) were associated with reduced risk of ovarian cancer. In contrast, the C allele of rs743572 in CYP17A1 (OR 1.54; 95% CI: 1.29-1.84; P < 0.0001) was associated with increased risk. Despite promising findings, the limited number of studies and population heterogeneity may impact the robustness and generalizability of the results. These findings suggest a possible role for these polymorphisms in ovarian cancer risk and highlight the need for further studies. This review was registered in PROSPERO (CRD42023464116).