Genetic Risk and Gynecologic Cancers

HBOC syndrome

HBOC syndrome is caused by mutations in the BRCA1 or BRCA2 genes, which were first identified and cloned in the early 1990s.4, 5 The prevalence of mutations in BRCA1 and BRCA2 among the general population has been estimated to be as high as 1 in 400.⁶ However, this varies among different populations. In certain populations that have undergone a period of relative isolation, founder mutations in BRCA1 and BRCA2 have been identified. For example, Ashkenazi Jews have a prevalence of approximately

Lynch syndrome

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, accounts for most inherited endometrial cancer cases. The original family was described in 1913 by Aldred Warthin, although the syndrome was not characterized until the 1960s and 1970s.78, 79, 80 Since that time, Lynch syndrome has been recognized as an inherited mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). The prevalence of these mutations in the general population is

Other syndromes

Several other rare hereditary cancer syndromes have gynecologic manifestations, including Peutz-Jeghers syndrome (PJS), Cowden syndrome (CS), and Li-Fraumeni syndrome (LFS). Given their rarity, there are few data regarding screening, prognosis, and treatment.

Pigmented lesions on the lips and buccal mucosa, as well as increased risk for tumors and malignancies at multiple sites, including the breast, gastrointestinal system, and the gynecologic organs, characterize PJS. PJS results from germline

Summary

Although most gynecologic malignancies are sporadic, hereditary cancer syndromes cause a substantial portion of these cancers. Given that the diagnosis of these syndromes has prognostic and therapeutic implications for the patient, as well as preventive implications for her family members, genetic testing is now an accepted part of the management of the patient who has gynecologic cancer.