A Systematic Review of the Molecular Mechanisms Involved in the Association Between PCOS and Endometrial and Ovarian Cancers.

Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA. This is achieved by conducting a thorough literature review and utilising specific search terms to identify all relevant studies published in English from 2010 to December 2022. PRISMA was followed, and the protocol was registered on PROSPERO (CRD42022375461). The QUADAS-2 tool and Review Manager Software were employed to evaluate study quality and risk of bias respectively. Forty-five eligible studies were selected with molecular signatures based on genomic, transcriptomic, metabolomic, proteomic and epigenetic analyses. Genes and their products deregulated in EC and/or OVCA were identified, including BRCA1, MLH1, NQO1 and ESR1, which were also deregulated in PCOS. Serum levels of IGF1, IGFBP1, SREBP1 and visfatin in women with PCOS were also identified as potential biomarkers of enhanced EC risk. Salusin-β serum levels in individuals with PCOS were identified as a potential biomarker for increased risk of OVCA. Gene signature-based drug repositioning identified several drug candidates: metformin, fenofibrate, fatostatin, melatonin, resveratrol and quercetin, some already established and prescribed for PCOS. In conclusion, this study provides a strong basis for further research to confirm the identified molecular signatures and associated causal links for potential therapeutic prevention strategies for EC and OVCA in women with PCOS.