Genetic Disorders Requiring Risk-Reducing Surgical Management in Our Gynecological Oncology Practice

Abstract

Cancer occurs as a result of the mutations in genes that are responsible for cell development and DNA integrity. Mutations can occur in germ cells (germline) (GLM) as well as others (somatic) (SM). GLM are responsible for 5-10% of cancers. Early detection of GLMs is critical for identifying at-risk individuals, following up, and designing risk-reducing procedures. Furthermore, the detection of SM in tumor tissue has recently been used to determine the necessity for extra adjuvant and targeted therapy. Although familial clustering is observed in 10-30% of ovarian (OC) and breast (BC) cancer cases. GLM in the BRCA1/2, which cause DNA repair deficiencies, are responsible for 65-85% of genetic anomalies in hereditary OC. Risk-reducing mastectomy (RRM) reduces the risk of BC by about % 90-95 in cases with pathogenic mutations (PMs) in the BRCA1/2 genes, while risk-reducing salpingo-oophorectomy (RRSO) reduces the incidence of BC (%50 ) and OC(%70-96 ), as well as a decrease in overall cancer-specific mortality. Except for BRCA1/2, OC is caused by PMs in genes like RAD51C, RAD51D and BRIP1, which affect DNA repair process. RRSO is indicated among carriers of PMs in these genes. Lynch syndrome (LS) is associated with a higher risk of colorectal and endometrial cancer. After completing their fertility, hysterectomy and bilateral RRSO are recommended for carriers of PMs in the MLH1, MSH2, and MSH6 genes. Based on the most recent guidelines, our goal in this review is to highlight the genetic alterations that necessitate risk-reducing prophylactic surgical procedures, which are becoming more common in our gynecological oncology practice.