BRCA1 Sequence Analysis in Women at High Risk for Susceptibility Mutations

摘要: Octext. —A mutation in theBRCA1gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between factors is incomplete. Objectives. —To identifyBRCA1mutations to determine that best predict presence of a deleteriousBRCA1mutation patients with Design. complete sequence analysis theBRCA1coding flanking intronic regions was performed 798 women collaborative effort involving institutions from United States, Italy, Germany, Finland, Switzerland. Participanta. —Institutions selected persons representing families (1 person each family) thought be at elevated priori ofBRCA1mutation due potential factors, such as multiple cases cancer, early age cancer diagnosis, No participant family which genetic markers showed linkage theBRCA1locus. Major Outcome Measures. —Sequence variants detected this sample are presented along analyses designed predictive characteristics those testing positive forBRCA1mutations. Results. —In 102 (12.8%), clearly deleterious were detected. Fifty new alterations found including 24 mutations, unknown significance, 2 rare polymorphisms. In subset 71 Ashkenazi Jewish women, only distinct found: 185delAG 17 5382insC 7 cases. A bias prior reports exon 11 revealed. Characteristics patient's specific diagnosis (unilateral or bilateral without cancer), ethnicity, history positively associated probability her carrying deleteriousBRCA1mutation. Conclusions. —Using logistic regression analysis, we provide method evaluating woman's wide range cases, can an important tool clinicians they incorporate susceptibility into their medical practice.