The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%

Abstract

Certain germline mutations in either BRCA1 or BRCA2 confer a lifetime risk of developing breast cancer that may approach 90%. The BRCA1 185delAG mutation was found in 20% and the BRCA2 6174delT mutation in 8% of Ashkenazi Jewish women with early-onset breast cancer. The 185delAG mutation was observed in 0.9% of 858 Ashkenazi Jews unselected for a personal or family history of cancer. Assuming comparable age-specific penetrances, a carrier frequency of 0.3% was estimated for the 6174delT BRCA2 mutation. To test this hypothesis, we performed a population survey of 1,255 Jewish individuals. In two independent groups, a prevalence of approximately 1% (C.I. 0.6-1.5) was observed for the 6174delT mutation. The relative risk of developing breast cancer by age 42 was estimated to be 9.3 (C.I. 2.5-22.5) for 6174delT, compared to 31 (C.I. 11-77) for 185delAG. Analysis of 107 Ashkenazi Jewish women with breast cancer and a family history of breast or ovarian cancer confirmed a four-fold greater prevalence for the BRCA1 185delAG mutation compared to the BRCA2 6174delT mutation. Our findings suggest a difference in cumulative life-time penetrance for the two mutations. Genetic counseling for the one in 50 Ashkenazi Jewish individuals harbouring specific germline mutations in BRCA1 or BRCA2 must be tailored to reflect the different risks associated with the two mutations.

The role of BRCA1 and BRCA2 in prostate cancer

“…It has been estimated that ,2% of this population carries at least one of these mutations. [77][78][79][80] Even in this population, the results of these epidemiological studies have been contradictory, but many of them were underpowered, due to small sample size or lack of covariate information. 22,[81][82][83][84][85][86] Another BRCA2 founder mutation that has been extensively studied is the Icelandic BRCA2 999del5 mutation.…”

Identification of two distinct deleted regions on chromosome 13 in prostate cancer

“…So far two tumor suppressor genes (TSG) have been identi®ed on this chromosome: the retinoblastoma gene (Rb1) on 13q14.2 and the breast cancer susceptibility locus 2 (BRCA2) on 13q12.1 (Lee et al, 1987;MacGee et al, 1989;Wooster et al, 1995). Rb1 is a cell cycle regulator which is involved in both hereditary and sporadic retinoblastoma, while BRCA2 mutations have been described in a subset of families with site speci®c breast cancer only (Oddoux et al, 1996;Phelan et al, 1996;Thorlacius et al, 1996;Wooster et al, 1995;.…”

Cancer Genetics Knowledge and Beliefs and Receipt of Results in Ashkenazi Jewish Individuals Receiving Counseling for BRCA1/2 Mutations

“…5 The presence of risk factors, such as a personal and/or family history of breast or ovarian cancer and multiple generations affected, increases the risk of having a mutation. 2,6 Hence, these mutations occur at a higher frequency in the Ashkenazi Jewish population than in the general population and represent a significant health threat due to their association with cancer. …”