Racial and Ethnic Differences in Multigene Hereditary Cancer Panel Test Results for Women With Breast Cancer
Siddhartha Yadav, Holly LaDuca, Eric C. Polley, Chunling Hu, Nancy Niguidula, Hermela Shimelis, Jenna Lilyquist, Jie Na, Kun Y. Lee, Stephanie Gutierrez, Amal Yussuf, Steven N. Hart, Brigette Tippin Davis, Elizabeth Chao, Tina Pesaran, David E. Goldgar, Jill S. Dolinsky, Fergus J. Couch
Abstract
To evaluate the racial and ethnic differences in prevalence of germline pathogenic variants (PVs) and the effect of race and ethnicity on breast cancer (BC) risk among carriers, results of multigene testing of 77 900 women with BC (non-Hispanic White [NHW] = 57 003; Ashkenazi-Jewish = 4798; Black = 6722; Hispanic = 5194; and Asian = 4183) were analyzed, and the frequency of PVs in each gene were compared between BC patients (cases) and race- and ethnicity-matched gnomAD reference controls. Compared with NHWs, BRCA1 PVs were enriched in Ashkenazi-Jews and Hispanics, whereas CHEK2 PVs were statistically significantly lower in Blacks, Hispanics, and Asians (all 2-sided P < .05). In case-control studies, BARD1 PVs were associated with high risks (odds ratio > 4.00) of BC in Blacks, Hispanics, and Asians; ATM PVs were associated with increased risk of BC among all races and ethnicities except Asians, whereas CHEK2 and BRIP1 PVs were associated with increased risk of BC among NHWs and Hispanics only. These findings suggest a need for personalized management of BC risk in PV carriers based on race and ethnicity.