BRCA ۱/۲ mutations and risk of uterine cancer: a systematic review and meta-analysis

Uterine cancer risk in BRCA۱/۲m women and its significance in the BRCA mutated condition are still beyond controversy. The similarities between serous ovarian and uterine cancers, especially serous carcinomas, have prompted researchers to look for shared pathogenetic traits as well as hereditary factors. ۱۰% of the cases of endometrial cancer are found to have positive family histories, suggesting a genetic tendency. BRCA۱/۲ are both autosomal dominant tumor suppressor genes involved in DNA damage repair prior to cell replication. BRCA۱ and BRCA۲ mutation carriers’ risk of developing uterine cancer is still unknown due to inconsistent results from various studies that may have been impacted by past tamoxifen treatment. However, the majority of research has indicated an approximately two-fold increase in risk compared to the general population. BRCA۱-associated endometrial cancers are associated with an unfavorable outcome and it requires additional studies to confirm findings. Method: We systematically searched three databases including PubMed, Scopus, and Google Scholar up to August ۲۰۲۳; and reviewed ۲۳ cohorts and cross-sectional studies to explore the association between BRCA۱/۲ mutations and uterine cancer incidence. Results: ۲۳ full-text articles evaluated the relevance of BRCA۱/۲ mutations in individuals with uterine and endometrial cancer were included in the systematic review after screening the articles. This systematic review included almost ۲۶,۰۰۰ patients in total. The studies had a patient population ranging from ۷ to ۳۶۲۳ for endometrial cancer and g from ۸۲۸ to ۵۹۸۰ for uterine cancer. ۳.۳ to ۱۴ years were covered by the median follow-up. The prevalence of BRCA mutation varied from ۰% to ۲۷.۲%. According to meta-analysis the prevalence of the BRCA۱/۲ gene in patients with uterine cancer was ۰.۰۲ (۹۵%CI = [۰.۰۱,۰.۰۳], I۲=۹۴.۸۲%, p<۰.۰۱). Discussion: Gene mutations are thought to be the main cause of about ۵% of cases of endometrial cancer. Characterizing somatic genetic changes in uterine cancer has received a lot of attention in the last ten years, but uterine cancer’s molecular causes are not yet well understood. Such uterine cancers exhibit similar molecular and morphological characteristics, indicating the potential of a connection to hereditary breast and ovarian cancer and the BRCA۱ mutation. Numerous studies have found that UPSC patients have a high prevalence of BRCA mutations and that BRCA mutation carriers have a higher risk of developing UPSC, but some other results do not corroborate these results. Furthermore, we did a reverse analysis of prospective research to determine the risk of uterine cancer in BRCA mutation carriers. Compared to the general population, women with a deleterious BRCA۱ or BRCA۲ mutation had a roughly ۲.۵-fold greater risk of getting uterine cancer, according to the cohort study on the rate of BRCA mutation in uterine cancer. Conclusion: Our meta-analysis investigates ۲% prevalence of BRCA۱/۲ mutation in patients with uterine cancer. Patients with BRCA۱/۲ mutations might be more conscious of uterine malignancies. Our findings might help physicians enhance therapy options for USC patients by including targeted therapies and preventing and genetic guidance. Large scaled observational studied are needed to further support this articles results

کلیدواژه ها:

BRCA۱ ، BRCA۲ ، Mutation ، Uterine cancer ، Endometrial