TY - JOUR
T1 - BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer
AU - Moslehi, Roxana
AU - Chu, William
AU - Karlan, Beth
AU - Fishman, David
AU - Risch, Harvey
AU - Fields, Abbie
AU - Smotkin, David
AU - Ben-David, Yehuda
AU - Rosenblatt, Jacalyn
AU - Russo, Donna
AU - Schwartz, Peter
AU - Tung, Nadine
AU - Warner, Ellen
AU - Rosen, Barry
AU - Friedman, Jan
AU - Brunet, Jean Sébastien
AU - Narod, Steven A.
N1 - Funding Information:
We thank all of the patients and their families, without whose kind cooperation this study would not have been possible. We thank Michelle Kelly-Dicanio, Myrna Ben Yaashay, Aimee Wonderlick, and Elaine Ball for their assistance in obtaining blood samples and epidemiological information on some of the patients. Technical assistance by John Abrahamson, Jalil Hakimi, Elaine Jack, Elaine Kwan, and Graciela Kuperstein is much appreciated. We also thank J. M. Friedman, Meri Klein, Marianna Gorbataia, Elizabeth Hoodfar, Alexander Liede, and Eva Weinroth. This study was supported by grants from the NIH (RO1CA 63678-05), the United States Army (DAMD 17-94-J-4299), the Canadian Genetic Disease Network, and the Canadian Breast Cancer Research Initiative.
PY - 2000
Y1 - 2000
N2 - Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in ~2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 4.1.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P = .002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P = .0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.
AB - Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in ~2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 4.1.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P = .002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P = .0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.
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U2 - 10.1086/302853
DO - 10.1086/302853
M3 - Article
C2 - 10739756
AN - SCOPUS:0033927850
SN - 0002-9297
VL - 66
SP - 1259
EP - 1272
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -