Hereditary Gynecologic Cancer Predisposition: Gene-Specific Risk Assessment, Genetic Counseling, and Personalized Prevention Strategies
DOI:
https://doi.org/10.64784/340Palabras clave:
hereditary gynecologic cancer, BRCA1, BRCA2, Lynch syndrome, genetic counseling, germline testing, cascade testing, ovarian cancer, endometrial cancer, risk-reducing surgery, precision prevention, cancer geneticsResumen
Hereditary gynecologic cancer syndromes constitute a heterogeneous group of disorders in which pathogenic germline variants increase susceptibility to ovarian, fallopian tube, endometrial, and other related malignancies. This study analyzed current evidence regarding the clinical identification of individuals at increased hereditary risk, molecular testing, genetic counseling, cascade testing, and strategies for cancer risk reduction. A structured integrative review based on the Scientific Method was performed using clinical guidelines, consensus recommendations, prospective cohorts, observational studies, and relevant genetic risk analyses. The results demonstrated substantial gene-specific variability. Cumulative ovarian cancer risk was markedly higher among BRCA1 carriers than among BRCA2 carriers, while moderate-penetrance genes such as BRIP1, RAD51C, and RAD51D showed lower but clinically relevant risk estimates. Lynch syndrome also exhibited heterogeneous gynecologic cancer patterns across MLH1, MSH2, MSH6, and PMS2. The reviewed evidence further identified an important gap between recommendations for genetic evaluation and actual completion of germline or somatic testing in patients with ovarian cancer. Risk-reducing salpingo-oophorectomy was associated with lower ovarian cancer occurrence and reduced cancer-specific and all-cause mortality among selected BRCA1/2 carriers. These findings support an individualized model of hereditary gynecologic cancer management based on integration of clinical history, family history, molecular diagnosis, gene-specific penetrance, genetic counseling, and preventive interventions. Effective hereditary cancer prevention depends not only on identifying pathogenic variants but also on translating genetic information into timely, proportionate, and patient-centered clinical decisions.
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