A Population-Based Study of Genes Previously Implicated in Breast Cancer
Chunling Hu, Steven N. Hart, Rohan Gnanaolivu, Hongyan Huang, Kun Y. Lee, Jie Na, Chi Gao, Jenna Lilyquist, Siddhartha Yadav, Nicholas Boddicker, Raed Samara, Josh Klebba, Christine B. Ambrosone, Hoda Anton‐Culver, Paul L. Auer, Elisa V. Bandera, Leslie Bernstein, Kimberly A. Bertrand, Elizabeth S. Burnside, Brian D. Carter, Heather Eliassen, Susan M. Gapstur, Mia M. Gaudet, Christopher A. Haiman, James M. Hodge, David J. Hunter, Eric J. Jacobs, Esther M. John, Charles Kooperberg, Allison W. Kurian, Loı̈c Le Marchand, Sara Lindströem, Tricia Lindstrom, Huiyan Ma, Susan L. Neuhausen, Polly A. Newcomb, Katie M. O’Brien, Janet E. Olson, Irene M. Ong, Tuya Pal, Julie R. Palmer, Alpa V. Patel, Sonya Reid, Lynn Rosenberg, Dale P. Sandler, Christopher J. Scott, Rulla M. Tamimi, Jack A. Taylor, Amy Trentham‐Dietz, Celine M. Vachon, Clarice R. Weinberg, Song Yao, Argyrios Ziogas, Jeffrey N. Weitzel, David E. Goldgar, Susan M. Domchek, Katherine L. Nathanson, Peter Kraft, Eric C. Polley, Fergus J. Couch
Abstract
BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: , were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).