Incidence of BRCA1 and BRCA2 non-founder mutations in patients of Ashkenazi Jewish ancestry
| Autor: | Brent Evans, Kelsey Moyes, Richard J. Wenstrup, Christopher Arnell, Eric Rosenthal |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty endocrine system diseases Population Breast Neoplasms medicine.disease_cause Breast cancer Risk Factors Internal medicine Medicine Humans Genetic Predisposition to Disease Genetic Testing Family history skin and connective tissue diseases education Genetic testing Genetics BRCA2 Protein Ovarian Neoplasms Mutation education.field_of_study medicine.diagnostic_test business.industry BRCA1 Protein Incidence (epidemiology) Cancer medicine.disease Ashkenazi jews Oncology Jews Female business |
| Zdroj: | Breast cancer research and treatment. 149(1) |
| ISSN: | 1573-7217 |
| Popis: | An estimated 1:40 individuals of Ashkenazi Jewish (AJ) ancestry carry one of three common founder mutations in BRCA1 or BRCA2, resulting in the inherited cancer condition, Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Targeted testing for these three mutations (BRCA1 187delAG, BRCA1 5385insC, and BRCA2 6174delT) is therefore recommended for all AJ breast and ovarian cancer patients, regardless of age of diagnosis or family history. Comprehensive analysis of both genes is recommended for a subset of AJ patients in whom founder mutations are not identified, but estimates of the yield from comprehensive analysis in this population vary widely. We sought to determine the proportion of non-founder mutations as a percentage of all mutations in BRCA1 and BRCA2 among AJ patients to inform decisions about HBOC testing strategies in this population. We analyzed the genetic testing results for 37,952 AJ patients for whom clinical testing of BRCA1 and BRCA2 was performed at Myriad Genetic Laboratories from January 2006 through August 2013. Analysis was limited to AJ-only patients for whom the initial test order was either (1) comprehensive testing, or (2) founder mutation testing with instructions to automatically “reflex” to comprehensive analysis if negative. Cases were excluded if a separate follow-up order was placed to reflex to comprehensive analysis only after the founder mutation testing was reported out as negative. Among all BRCA1 and BRCA2 mutations detected in these groups, the percentage of non-founder mutations was 13 % (104/802) and 7.2 % (198/2,769). One-hundred and eighty-nine unique non-founder mutations were detected, 76 in BRCA1 and 113 in BRCA2. Non-founder mutations make up between 7.2 and 13.0 % of all BRCA1 and BRCA2 mutations in Ashkenazi Jews. A wide range of mutations are present, most of which are also seen in non-AJ individuals. |
| Databáze: | OpenAIRE |
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