Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women

Julie R. Palmer, Eric C. Polley, Chunling Hu, Esther M. John, Christopher Haiman, Steven N. Hart, Mia Gaudet, Tuya Pal, Hoda Anton-Culver, Amy Trentham-DIetz, Leslie Bernstein, Christine B. Ambrosone, Elisa V. Bandera, Kimberly A. Bertrand, Traci N. Bethea, Chi Gao, Rohan D. Gnanaolivu, Hongyan Huang, Kun Y. Lee, Loic LemarchandJie Na, Dale P. Sandler, Payal D. Shah, Siddhartha Yadav, William Yang, Jeffrey N. Weitzel, Susan M. Domchek, David E. Goldgar, Katherine L. Nathanson, Peter Kraft, Song Yao, Fergus J. Couch

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies. Methods: Germline DNA samples were sequenced for mutations in 23 cancer predisposition genes using a QIAseq multiplex amplicon panel. Prevalence of mutations and odds ratios (ORs) for associations with breast cancer risk were estimated with adjustment for study design, age, and family history of breast cancer. Results: Pathogenic mutations were identified in 10.3% of women with estrogen receptor (ER)-negative breast cancer, 5.2% of women with ER-positive breast cancer, and 2.3% of unaffected women. Mutations in BRCA1, BRCA2, and PALB2 were associated with high risks of breast cancer (OR = 47.55, 95% confidence interval [CI] = 10.43 to >100; OR = 7.25, 95% CI = 4.07 to 14.12; OR = 8.54, 95% CI = 3.67 to 24.95, respectively). RAD51D mutations were associated with high risk of ER-negative disease (OR = 7.82, 95% CI = 1.61 to 57.42). Moderate risks were observed for CHEK2, ATM, ERCC3, and FANCC mutations with ER-positive cancer, and RECQL mutations with all breast cancer. Conclusions: The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.

Original languageEnglish (US)
Pages (from-to)1213-1221
Number of pages9
JournalJournal of the National Cancer Institute
Issue number12
StatePublished - Dec 1 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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