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.
- Diagnosis of cancer made at MSKCC or collaborating institutions, AND
- Tissue block of tumor or normal margin or extracted DNA available for study and
sufficient material present to allow study without exhausting block or DNA,
- Individual self-identified as Jewish on intake.
Kenneth Offit, M.D.
Memorial Sloan Kettering Cancer Center
Kenneth Offit, M.D.