Frequency ofBRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases

Abstract

BACKGROUND There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population‐based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes. METHODS Subjects were drawn from two population‐based, case‐control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first‐degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features. RESULTS Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first‐degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma. CONCLUSIONS Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations. Cancer 2000;88:1393–1402. © 2000 American Cancer Society.

Breast Cancer in Young Women from a Low Risk Population in Nepal

“…Indeed, in the present series younger women were likely to have a family history than women in the older group (3% vs 0.3%). Although we do not know the genetic status of our patients, approximately 5% of young patients had a germ-line BRCA1 mutation and a 3% BRCA2 mutation (Malone et al, 2000).…”

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital‐based screening

“…31 In the United States, different studies have demonstrated a clear prevalence of BRCA1 mutations. 32,33 In Table 6, the frequencies of BRCA1 and BRCA2 germline mutations among different populations are reported.…”

Polymorphisms in Second Intron of the FGFR2 Gene Are Associated with the Risk of Early-Onset Breast Cancer in Chinese Han Women

“…Except for genetic predisposition the risk factors for early-onset breast cancer remain to be determined, but may include high body mass index (BMI), Hodgkin's lymphoma, early age at menarche, and early age at first birth (althius and Brogan 2003; Silvera et al 2006;Rodriguez et al 2008;alm El-Din et al 2009). A study conducted within an American population showed that among early-onset breast cancer patients, only ~10% carried deleterious BRCA1 or BRCA2 mutations, and 1% were non-familial (Malone et al 2000). In China, BRCa1 and BRCa2 disease-causing mutations are responsible for ~3% and 0%, respectively, of early-onset breast cancers without a family history of breast or ovarian cancer (Li et al 2007;Ma et al 2008;Chen et al 2009).…”