Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals
| Autor: | Thomas S. Frank, Amie M. Deffenbaugh, Julia E. Reid, Mark Hulick, Brian E. Ward, Beth Lingenfelter, Kathi L. Gumpper, Thomas Scholl, Sean V. Tavtigian, Dmitry R. Pruss, Gregory C. Critchfield |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
BRCA2 Protein Male Ovarian Neoplasms Cancer Research Chi-Square Distribution endocrine system diseases DNA Mutational Analysis Genes BRCA1 Breast Neoplasms Founder Effect Breast Neoplasms Male Neoplasm Proteins Oncology Risk Factors Jews Humans Female Genetic Predisposition to Disease Genetic Testing skin and connective tissue diseases Germ-Line Mutation |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 20(6) |
| ISSN: | 0732-183X |
| Popis: | PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting. PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex. RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P = .0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1. CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting. |
| Databáze: | OpenAIRE |
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