Anonymous Testing of Pathology Specimens for BRCA Mutations in Ashkenazi Jewish Individuals Who Have Cancer

Overview

The intent of the proposed study is to describe the prevalence of the most common recurring mutations in BRCA1 and BRCA2, blmAsh , and the A636P MSH2 mutation among Ashkenazi Jewish individuals with a variety of cancer diagnoses. If a substantial proportion of these samples contain such mutations, future patients presenting with these diseases may wish to undergo genetic counseling and, if appropriate, formal genetic testing. The benefit from such a process would pertain mainly to the families of these individuals.

Germline mutations in the genes BRCA1 and BRCA2 have been demonstrated in the majority of hereditary breast and ovarian cancer families. The increased risk to develop both breast and ovarian cancer associated with inheriting a BRCA1 or BRCA2 mutation has been well established. It has also been suggested that is an overrepresentation of other cancers such as colon, prostate and pancreatic cancer present in BRCA1 or BRCA2 families. Population specific mutations in BRCA1 and BRCA2 have been identified. In the Ashkenazi Jewish population, 3 specific mutations have been seen in 2% of the population. This study will anonymously screen archived tissue samples of Ashkenazi Jewish individuals diagnosed with cancer between 1993 and 1996 at MSKCC for the three founder mutations seen in the Ashkenazi Jewish population. Results will be stratified by tumor type and compared with the population frequency to determine whether individuals inheriting mutations in BRCA1 or BRCA2 may have an increased risk to develop other cancers, in addition to breast and ovarian cancer. This information will be useful in helping to identify individuals who may benefit from genetic counseling and possibly genetic testing who to date are not typically referred. It will also be useful in developing high-risk cancer screening strategies and determining appropriate options for prophylactic surgery.

Conditions