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 LeMarchand; Jie 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

doi:10.1093/jnci/djaa040

Journal article

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, …

JNCI : Journal of the National Cancer Institute, Vol.112(12), pp.1213-1221

12/01/2020

DOI: https://doi.org/10.1093/jnci/djaa040

PMID: 32427313

Abstract

Abstract 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.

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Title: Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women
Creators: Julie R Palmer - Department of Medicine, Boston University School of Medicine, and Slone Epidemiology Center, Boston, MA 02118, USA
Eric C Polley - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Chunling Hu - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Esther M John - Department of Health Research & Policy, Stanford University School of Medicine, Stanford, CA 94305, USA
Christopher Haiman - Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA
Steven N Hart - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Mia Gaudet - Epidemiology Research, American Cancer Society, Atlanta, GA 30303, USA
Tuya Pal - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Hoda Anton-Culver - Department of Medicine, UC Irvine, Irvine, CA 92697, USA
Amy Trentham-Dietz - Department of Population Health Sciences and Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53726, USA
Leslie Bernstein - Department of Population Sciences, City of Hope, Duarte, CA 91010, USA
Christine B Ambrosone - Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
Elisa V Bandera - Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New, New Brunswick, NJ 08903, USA
Kimberly A Bertrand - Department of Medicine, Boston University School of Medicine, and Slone Epidemiology Center, Boston, MA 02118, USA
Traci N Bethea - Department of Medicine, Boston University School of Medicine, and Slone Epidemiology Center, Boston, MA 02118, USA
Chi Gao - Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Rohan D Gnanaolivu - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Hongyan Huang - Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
Kun Y Lee - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Loic LeMarchand - Population Sciences in the Pacific Program (Cancer Epidemiology), University of Hawaii Cancer Center Honolulu, HI 96813, USA
Jie Na - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Dale P Sandler - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Payal D Shah - Abramson Cancer Center and Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA 19104, USA; and 16Department of Dermatology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Siddhartha Yadav - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
William Yang - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Jeffrey N Weitzel - Department of Population Sciences, City of Hope, Duarte, CA 91010, USA
Susan M Domchek - Abramson Cancer Center and Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA 19104, USA; and 16Department of Dermatology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
David E Goldgar - Department of Medicine, Boston University School of Medicine, and Slone Epidemiology Center, Boston, MA 02118, USA
Katherine L Nathanson - Abramson Cancer Center and Basser Center for BRCA, University of Pennsylvania, Philadelphia, PA 19104, USA; and 16Department of Dermatology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
Peter Kraft - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Song Yao - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Fergus J Couch - Departments of Health Sciences Research, Laboratory Medicine and Pathology, and Oncology, Mayo Clinic, Rochester, MN 55902, USA
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.112(12), pp.1213-1221
Date published: 12/01/2020
Publisher: Oxford University Press
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665956404646