Cancer Control Research
5U01CA058860-08
Anton-Culver, Hoda A.
HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIES
AbstractA major risk factor for breast cancer is family history of the disease.
Original estimates suggested that 50 percent of the cases of familial
breast cancer have BRCAI and/or BRCM mutations. Further, the majority
of families with breast and ovarian cancer have mutations in BRCAI.
However, the frequency of BRCA mutations is not fully understood in
families with a modest cancer phenotype or where other tumors occur in
combination with breast. In particular Familial breast and ovarian
cancer, familial breast and colon cancer and familial breast and
prostate cancer are three combinations where each is known own to share
common risk factors, molecular-genetic predisposition and/or shared
etiologic biological plausibility. This is an application for renewal
of our existing NCI project of the same name (1, U0l CA58860-04),
converted from an R01 as of January 1997. To date, our current project
includes population based breast (1270) and ovarian (262) cancer
probands. Pedigree data on first- and second-degree relatives and
first-cousins, pathology data, clinical information, epidemiologic risk
and diet data, blood and tissue specimens and laboratory results are
available on all probands. There will be no further ascertainment of new
probands in this proposed project. The overall goal of this project is
to maintain and follow up the existing family resource, further
characterize BRCA mutations in breast and ovarian cancer families and
explore the associated functions of BRCA1 missense mutations. In
addition, we will determine whether there is molecular genetic evidence
for the aggregation of breast and colorectal cancer in a subgroup of the
existing high risk breast cancer families. There is strong Familial and
molecular genetic evidence of an association between breast and ovarian
cancer and also a familial association between breast and colon cancer.
Further, we have preliminary results that show mutations in MSH2 and
MLH1 in breast cancer families where there is colon cancer in first or
second degree relatives. It is important, therefore, that candidate
genes (such as mismatch repair genes) relevant to the tumor spectrum in
these families in addition to BRCA1 and BRCA2 be examined and possible
new genetic alterations be explored. The data generated from the
proposed study will have future clinical applications particularly for
subjects from breast cancer families, possessing the diverse spectrum
of tumors as is often observed in familial breast cancer.
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