Gynecologic malignancies in Ashkenazi families with the MSH2 A636P founder mutation.

Objective: A founder mutation A636P in the MSH2 gene was found to be related to hereditary nonpolyposis colorectal cancer in Ashkenazi Jews. Although the incidence of colorectal cancer in carriers is relatively well established, the frequency of other tumors is less clear.

Study Design: We studied a consecutive series of 19 carrier families that were cared for by the Clalit Health Studies National Familial Cancer Consultation Service, most of whom were identified through a population-based case-control study of colorectal cancer in northern Israel.

Results: Gynecologic cancers, 88% of which (28 cases) were endometrial cancers, were diagnosed in 78.9% of the carrier families and in 26.2% of the women who were at risk, with a mean age at diagnosis of 51.2 years. Forty-six percent of the women with endometrial cancer reported at least 1 other primary tumor.

Conclusion: Genetic counseling and testing for the MSH2 A636P mutation is indicated for Ashkenazi Jewish women with an endometrial cancer, especially if the cancer is detected before the age of 70 years in women with a personal or family history of colorectal cancer.