Dataset Information

Breast and ovarian cancer penetrance of BRCA1/2 mutations among Hong Kong women.

ABSTRACT: Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are associated with increased risk of breast and ovarian cancer. The penetrance of breast and ovarian cancer in BRCA1/2 mutation carriers has been well characterized in Caucasian but not in Asian. Two studies have investigated the breast cancer risk in Asian women with BRCA1/2 mutations, and no published estimates are available for ovarian cancer. Therefore, we estimated the age-specific cumulative risk of BRCA1/2-associated breast and ovarian cancer in Chinese women. From Jan 2007 to Nov 2015, the Hong Kong Hereditary Breast Cancer Family Registry identified 1635 families with hereditary breast-ovarian cancer. Among probands in these families, 66 had BRCA1 mutations, 84 had BRCA2 mutations, and 1,485 tested negative for BRCA1/2 mutations. Using the female first-degree relatives of these probands, we estimated the risk of breast and ovarian cancer using a modified marginal likelihood approach. Estimates of breast cancer penetrance by age 70 were 53.7% (95% CI 34.5-71.6%) for BRCA1 mutation carriers and 48.3% (95% CI 31.8-68.5%) for BRCA2. The estimated risk of ovarian cancer by age 70 was 21.5% and 7.3% for Chinese women carrying BRCA1 or BRCA2 mutation respectively. A meta-analysis of available studies in Asian women revealed pooled estimates of breast cancer risk by age 70 of 44.8% (95% CI 33-57.2%) and 40.7% (95% CI 31.3-50.9%) for BRCA1 and BRCA2 mutation carriers respectively. These data suggest that BRCA1/2-associated breast cancer risk for Chinese women is similar to that for Caucasian women, although BRCA1/2-associated ovarian cancer risks are lower for Chinese women.

SUBMITTER: Zhang L

PROVIDER: S-EPMC5982775 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Breast and ovarian cancer penetrance of BRCA1/2 mutations among Hong Kong women.

Zhang LingJiao L Shin Vivian Y VY Chai Xinglei X Zhang Alan A Chan Tsun L TL Ma Edmond S ES Rebbeck Timothy R TR Chen Jinbo J Kwong Ava A

Oncotarget 20180202 38

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are associated with increased risk of breast and ovarian cancer. The penetrance of breast and ovarian cancer in BRCA1/2 mutation carriers has been well characterized in Caucasian but not in Asian. Two studies have investigated the breast cancer risk in Asian women with BRCA1/2 mutations, and no published estimates are available for ovarian cancer. Therefore, we estimated the age-specific cumulative risk of BRCA ...[more]

PMID: 29861850

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Project description:A population-based series of 649 unselected incident cases of ovarian cancer diagnosed in Ontario, Canada, during 1995-96 was screened for germline mutations in BRCA1 and BRCA2. We specifically tested for 11 of the most commonly reported mutations in the two genes. Then, cases were assessed with the protein-truncation test (PTT) for exon 11 of BRCA1, with denaturing gradient gel electrophoresis for the remainder of BRCA1, and with PTT for exons 10 and 11 of BRCA2. No mutations were found in all 134 women with tumors of borderline histology. Among the 515 women with invasive cancers, we identified 60 mutations, 39 in BRCA1 and 21 in BRCA2. The total mutation frequency among women with invasive cancers, 11.7% (95% confidence interval [95%CI] 9.2%-14.8%), is higher than previous estimates. Hereditary ovarian cancers diagnosed at age <50 years were mostly (83%) due to BRCA1, whereas the majority (60%) of those diagnosed at age >60 years were due to BRCA2. Mutations were found in 19% of women reporting first-degree relatives with breast or ovarian cancer and in 6.5% of women with no affected first-degree relatives. Risks of ovarian, breast, and stomach cancers and leukemias/lymphomas were increased nine-, five-, six- and threefold, respectively, among first-degree relatives of cases carrying BRCA1 mutations, compared with relatives of noncarriers, and risk of colorectal cancer was increased threefold for relatives of cases carrying BRCA2 mutations. For carriers of BRCA1 mutations, the estimated penetrance by age 80 years was 36% for ovarian cancer and 68% for breast cancer. In breast-cancer risk for first-degree relatives, there was a strong trend according to mutation location along the coding sequence of BRCA1, with little evidence of increased risk for mutations in the 5' fifth, but 8.8-fold increased risk for mutations in the 3' fifth (95%CI 3.6-22.0), corresponding to a carrier penetrance of essentially 100%. Ovarian, colorectal, stomach, pancreatic, and prostate cancer occurred among first-degree relatives of carriers of BRCA2 mutations only when mutations were in the ovarian cancer-cluster region (OCCR) of exon 11, whereas an excess of breast cancer was seen when mutations were outside the OCCR. For cancers of all sites combined, the estimated penetrance of BRCA2 mutations was greater for males than for females, 53% versus 38%. Past studies may have underestimated the contribution of BRCA2 to ovarian cancer, because mutations in this gene cause predominantly late-onset cancer, and previous work has focused more on early-onset disease. If confirmed in future studies, the trend in breast-cancer penetrance, according to mutation location along the BRCA1 coding sequence, may have significant impact on treatment decisions for carriers of BRCA1-mutations. As well, BRCA2 mutations may prove to be a greater cause of cancer in male carriers than previously has been thought.

Dataset Information

Breast and ovarian cancer penetrance of BRCA1/2 mutations among Hong Kong women.

Publications

Breast and ovarian cancer penetrance of <i>BRCA1/2</i> mutations among Hong Kong women.

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