About BRCA 1 and BRCA 2

Research on families with very strong patterns of breast and ovarian cancer led to the discovery of BRCA1 on chromosome 17 and BRCA2 on chromosome 13. BRCA1 and BRCA2 are normal genes carried by all men and women. When functioning properly, these genes play a role in tumor suppression through cell cycle regulation and DNA damage repair. Research continues to learn more about the precise role of BRCA1 and BRCA2 within the cell. About 5-10 percent of EOC cases are attributable to inheritance of highly penetrant mutations in the breast/ovarian cancer susceptibility genes BRCA-1 and -2.

The clinical presentation of heritable EOC is similar to sporadic EOC, but tends to occur 10-15 years earlier than in the general population. It is estimated that over 50 percent of women with BRCA1 mutations who develop EOC do so before age 50 and all women with these mutations have about a 30-40 percent risk of developing EOC by age 70.

Clues suggesting that a BRCA1 or BRCA2 mutation may be running in a family include: early-onset breast cancer (before menopause) in two or more relatives in different generations, ovarian cancer in addition to breast cancer among relatives, bilateral breast cancer, breast and ovarian cancer in the same woman, and male relatives with breast cancer. Most families with very strong family histories of breast and ovarian cancer have mutations in the BRCA1 and BRCA2 genes. However, in some high-risk families and many families with more moderate clusters of breast and ovarian cancer, such cancers are not due to BRCA1 or BRCA2, suggesting the existence of other inherited susceptibility genes yet to be identified.

The importance of identifying families with hereditary cancer susceptibility becomes apparent given the significant cancer risks associated with BRCA1 and BRCA2 mutations. Women who carry a BRCA1 or BRCA2 mutation have a 5685 percent chance of developing breast cancer by age 70. The associated lifetime risk for ovarian cancer is 20-40 percent for BRCA1 mutations and 10-27 percent for BRCA2 mutations. In addition, BRCA2 mutations are associated with an increased risk of male breast cancer, and mutations in both genes may slightly increase the risk of prostate and colon cancer. Research continues to define the cancer spectrum associated with BRCA1 and BRCA2 mutations, and the magnitude of risk for each type of cancer.

In the general population of the U.S., approximately 1 in 400 individuals carries a BRCA1 or BRCA2 mutation. To date, several hundred different mutations predisposing to breast and ovarian cancer have been found in the BRCA1 and BRCA2 genes. However, certain mutations have been identified that are more common in individuals of particular ethnic backgrounds. Three founder mutations have been identified in Jewish individuals of Eastern European (Ashkenazi) ancestry. Ashkenazi Jewish women have an unexpectedly high frequency of a specific BRCA1 mutation compared with the general population. In the Ashkenazi Jewish population, about 2.5 percent have BRCA-1 or -2 mutations.

Approximately 1 in 40 Ashkenazi Jewish individuals carry one of these particular mutations, which is significantly higher than the general population. These mutations may account for 30-50 percent of all early-onset breast or ovarian cancer cases in this ethnic population. To date, research in which the Mount Sinai Ovarian Cancer Risk Assessment Program has participated suggests that up to 40 percent of Jewish women diagnosed with ovarian cancer and approximately 20 percent of Jewish women diagnosed with premenopausal breast cancer have a BRCA1 or BRCA2 mutation.

A less common cause of hereditary ovarian cancer occurs in association with the Hereditary Non-Polyposis Colon Cancer (HNPCC) syndrome. The most common features of HNPCC are early-onset colorectal cancer and endometrial cancer, although affected women also have a moderately increased risk of developing ovarian cancer (9-12 percent).

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Mount Sinai Ovarian Cancer Risk Assessment Program
Tel: 212-241-1111