Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer

Women's College Research Institute, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, Canada M5G 1N8.
Gynecologic Oncology (Impact Factor: 3.77). 02/2011; 121(2):353-7. DOI: 10.1016/j.ygyno.2011.01.020
Source: PubMed


The heritable fraction of ovarian cancer exceeds that of any other common adult cancer. Most inherited cases of ovarian cancer are due to a germline mutation in BRCA1 or BRCA2. It is important to have an accurate estimate of the proportion of ovarian cancer patients who carry a mutation and the specific factors which predict the presence of a mutation.
We tested a population-based series of 1342 unselected patients diagnosed with invasive ovarian cancer between 1995-1999 and 2002-2004 in Ontario, Canada, for germline mutations in BRCA1 and BRCA2. The two genes were tested in their entirety, using a range of techniques, including multiplex ligation-dependent probe amplification (MLPA).
Among the 1342 women, 176 women carried a mutation (107 in BRCA1, 67 in BRCA2, and two in both genes) for a combined mutation frequency of 13.3%. Seven deletions were identified using MLPA (3.9% of all detected mutations). The prevalence of mutations was particularly high among women diagnosed in their forties (24.0%), in women with serous ovarian cancer (18.0%) and women of Italian (43.5%), Jewish (30.0%) or Indo-Pakistani origin (29.4%). A mutation was seen in 33.9% of women with a first-degree relative with breast or ovarian cancer and in 7.9% of women with no first-degree relative with breast or ovarian cancer. No mutation was seen in women with mucinous carcinoma.
BRCA1 and BRCA2 mutations are common in women with invasive ovarian cancer. All women diagnosed with invasive non-mucinous ovarian cancer should be considered to be candidates for genetic testing.

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    • "Epithelial ovarian cancer is the most lethal gynecological malignancy . More than 10% of all epithelial ovarian cancers are inherited, mostly caused by a mutation in the BRCA1 or BRCA2 genes [1] [2] [3]. The lifetime risk of developing ovarian cancer at age 70 in women harboring a BRCA1 or BRCA2 mutation varies between 31–40% and 6–18%, respectively [4] [5], while the risk in the general population is 1.7%. "
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    ABSTRACT: To identify influencing factors of BRCA1/2 mutation carriers and their professionals for risk-reducing salpingectomy (RRS) with delayed oophorectomy (RRO) as a substitute for risk-reducing salpingo-oophorectomy (RRSO) and for study participation on this concept. A qualitative study was performed by four focus group interviews with 39 BRCA1/2 mutation carriers and semi-structured in-depth interviews with 23 professionals in the field of hereditary cancer. We used a theoretical framework of determinants of innovation within healthcare organizations to classify influencing factors (barriers and facilitators). Among BRCA1/2 mutation carriers, main barriers for RRS with delayed RRO were seriousness of ovarian cancer, family history, and previous breast cancer. Among professionals, delay of risk-reducing effect of oophorectomy on breast cancer risk and a second operation were recognized as main barriers. Both BRCA1/2 mutation carriers and professionals found uncertainty about the effect of RRS with delayed RRO and ease of the decision to undergo RRSO important barriers. The main facilitator mentioned by both was longer maintenance of ovarian function thereby delaying negative effects of early surgical menopause. For study participation, BRCA1/2 mutation carriers mentioned a randomized study design as the main barrier, whereas professionals identified two facilitators, namely willingness of BRCA1/2 mutation carriers for study participation and uniform counseling. Furthermore, most BRCA1/2 mutation carriers and professionals were willing to consider participation in a future non-randomized study. We identified several barriers and facilitators for RRS with delayed RRO, and for study participation which can be addressed to optimize the design and implementation of a non-randomized study. Copyright © 2014. Published by Elsevier Inc.
    No preview · Article · Jan 2015 · Gynecologic Oncology
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    • "Another large population-based study was conducted in Ontario, Canada: among 1342 unselected OC patients, 176 (13%) carried a BRCA1/2 mutation. Higher prevalence of mutations was associated with Italian, Jewish, or Indo- Pakistani origin, serous histology, younger age of onset, and, obviously, a family history of breast or ovarian cancer; among women without family history of such cancers, prevalence was 7.9% [48]. "
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    ABSTRACT: Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.
    Full-text · Article · Jul 2014 · BioMed Research International
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    • "We found that 16 % of unselected cases of ovarian cancer in Belarus carried one of three founder mutations in the BRCA1 gene. This is significant higher than in Canada or Poland [11, 12]. A reported family history was a strong predictor of the presence of a mutation, as was a young age of onset. "
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    ABSTRACT: In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend that all cases of ovarian cancer in Belarus be offered genetic testing for these founder mutations. Furthermore, genetic testing of the Belarusian population will provide the opportunity to prevent a significant proportion of ovarian cancer.
    Preview · Article · Apr 2014 · Familial Cancer
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