title: The genetic prediction of risk for gynecologic cancers.
abstract: Salient to the intent of personalized medicine, hereditary cancer syndromes present significant opportunities in the treatment and prevention of some gynecologic cancers. Mutations in BRCA1, BRCA2, and DNA mismatch repair genes: MLH1, MSH2, MSH6, and PMS2 are important causal agents in hereditary breast and ovarian cancer (HBOC) and Lynch syndromes. Though they only account for an estimated 10-18% of ovarian, tubal, peritoneal, and endometrial cancer cases, inherited cancers are imminently preventable if mutation carriers are identified in a timely manner. Population level screening is currently impractical due to low prevalence of disease, cost of testing, and ethical issues associated with testing, so diagnosis of these mutations is limited. Being affected by one of the heritable gynecologic malignancies is a logical entry point into the genetic counseling and testing pipeline for the patient and her family members. Thus, gynecologic cancer providers are uniquely positioned to diagnose germline mutations that can inform prognosis and treatment for their patients in addition to enabling prevention for patients' cancer-unaffected blood relatives, or "previvors". The purpose of this review is to describe our current perspective on testing for and implications of heritable cancer syndromes in the women with ovarian, tubal, peritoneal, and endometrial cancers.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine, 101 The City Dr. South, Bldg 56, Room 262, Orange, CA 92868. Electronic address: lrandall@uci.edu.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Randall
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, NYU Langone Medical Center, 240 E. 38th St., 19th floor, New York, NY 10016. Electronic address: Bhavana.Pothuri@nyu.edu.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Pothuri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000175:diagnosis; D003376:Counseling; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005833:Genital Neoplasms, Female / Q000209:etiology / Q000235:genetics*; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012306:Risk
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: BRCA; Lynch syndrome; ovarian cancer; precision medicine; risk-reduction; uterine cancer