R Institute, Department of Dermatology, University of Utah, Salt Lake City
R Institute, Department of Dermatology, University of Utah, Salt Lake City (Feng, Goldgar); Division of Clinical Diagnostics, Ambry Genetics Inc, Aliso Viejo, California (McFarland, Pesaran, Huether, LaDuca, Chao, Dolinsky); Now, Division of Genetics and Genomics, Department of Pediatrics, University of California-Irvine (Chao)AbstractImportance–Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime threat of breast cancer. On the other hand, the relevance of germline variants in other genes from multigene hereditary cancer testing panels isn’t effectively defined. Objective–To identify the risks of breast cancer linked with germline variants in cancer predisposition genes. Design, Setting, and Participants–A study population of 65 057 sufferers with breast cancer getting germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations among pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of individuals with breast cancer and Exome Aggregation Consortium reference controls. The girls underwent testing in between March 15, 2012, and June 30, 2016.Corresponding Author: Fergus J. Couch, PhD, Division of Laboratory Medicine and Pathology, Mayo Clinic, Stabile 2-42, 200 Initially St SW, Rochester, MN 55905 ([email protected]). Meeting Presentation: A portion of this analysis was presented in the 2016 San Antonio Breast Cancer Symposium; December 9, 2016; San Antonio, Texas. Author Contributions: Drs Couch, Shimelis, and Hu contributed equally to the study. Dr Couch and Ms Dolinsky had full access to each of the REG-3 alpha/REG3A, Human (HEK293, His) information inside the study and take responsibility for the integrity of the information plus the accuracy from the information evaluation. Study notion and design and style: Couch, Goldgar, Dolinsky. Acquisition, analysis, or interpretation of data: All authors., Drafting in the manuscript: Couch, Shimelis, Hu, LaDuca, Goldgar, Dolinsky., Vital revision on the manuscript for essential intellectual content: Couch, Shimelis, Hu, Polley, Na, Hallberg, Thomas, Lilyquist, Feng, McFarland, Pesaran, Huether, LaDuca, Chao, Goldgar, Dolinsky., Statistical analysis: Shimelis, Hart, Polley, Na, Lilyquist, Feng, Goldgar., Obtained funding: Couch., Administrative, technical, or material help: Couch, Hallberg, Moore, Thomas, McFarland, Huether, Dolinsky., Supervision: Couch, Hart, Chao, Goldgar, Dolinsky. Conflict of Interest Disclosures: Dr TGF beta 2/TGFB2, Mouse/Rat (HEK293)-1 Huether and Mss McFarland, Pesaran, LaDuca, and Dolinsky are employees of Ambry Genetics Inc. Dr Chao was employed by Ambry Genetics Inc at the time in the study. No other conflicts had been reported.Couch et al.PageMain Outcomes and Measures–Breast cancer danger conferred by pathogenic variants in nonBRCA1 and non-BRCA2 predisposition genes. Results–The mean (SD) age at diagnosis for the 65 057 girls included inside the evaluation was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white ladies with breast cancer was estimated at ten.2 . Right after exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN, and TP53), observed pathogenic variants in five of 16 genes have been related with higher or moderately elevated risks ofbreast cancer: ATM (OR, two.78; 95 CI, two.22-3.62), BARD1 (OR, two.16; 95 CI, 1.31-3.63), CHEK2 (OR, 1.48; 95 CI, 1.31-1.67), PALB2 (OR, 7.46; 95 CI, 5.12-11.19), and RAD51D (OR, 3.07; 95 CI, 1.21-7.88). Conversely, v.
