The contribution of pathogenic variants in breast cancer susceptibility genes to familial breast cancer risk NPJ BREAST CANCER Slavin, T. P., Maxwell, K. N., Lilyquist, J., Vijai, J., Neuhausen, S. L., Hart, S. N., Ravichandran, V., Thomas, T., Maria, A., Villano, D., Schrader, K. A., Moore, R., Hu, C., Wubbenhorst, B., Wenz, B. M., D'Andrea, K., Robson, M. E., Peterlongo, P., Bonanni, B., Ford, J. M., Garber, J. E., Domchek, S. M., Szabo, C., Offit, K., Nathanson, K. L., Weitzel, J. N., Couch, F. J. 2017; 3: 22


Understanding the gene-specific risks for development of breast cancer will lead to improved clinical care for those carrying germline mutations in cancer predisposition genes. We sought to detail the spectrum of mutations and refine risk estimates for known and proposed breast cancer susceptibility genes. Targeted massively-parallel sequencing was performed to identify mutations and copy number variants in 26 known or proposed breast cancer susceptibility genes in 2134 BRCA1/2-negative women with familial breast cancer (proband with breast cancer and a family history of breast or ovarian cancer) from a largely European-Caucasian multi-institutional cohort. Case-control analysis was performed comparing the frequency of internally classified mutations identified in familial breast cancer women to Exome Aggregation Consortium controls. Mutations were identified in 8.2% of familial breast cancer women, including mutations in high-risk (odds ratio?>?5) (1.4%) and moderate-risk genes (2??3.0, p?

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