Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women
Open Access
- 14 December 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 112 (12), 1213-1221
- https://doi.org/10.1093/jnci/djaa040
Abstract
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. 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. 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. 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.Funding Information
- National Institutes of Health (R01CA192393, R01CA225662, P50CA116201, U01CA164974, R01CA098663, R01CA100598, P01CA151135, P30CA16056, U01CA164973, U01CA164920, R01CA204819, R01CA77398, U01CA199277, P30CA014520, U01CA82004, R01CA047147, R01CA067264, American Cancer Society)
- Susan G. Komen Foundation
- Breast Cancer Research Foundation
- Karin Grunebaum Cancer Research Foundation
This publication has 62 references indexed in Scilit:
- Exome Sequencing Identifies Rare Deleterious Mutations in DNA Repair Genes FANCC and BLM as Potential Breast Cancer Susceptibility AllelesPLoS Genetics, 2012
- Lifetime Cancer Risks in Individuals with Germline PTEN MutationsClinical Cancer Research, 2012
- Rare variants in the ATMgene and risk of breast cancerBreast Cancer Research, 2011
- Underutilization of BRCA1/2 testing to guide breast cancer treatment: Black and Hispanic women particularly at riskGenetics in Medicine, 2011
- Health disparities in breast cancer: biology meets socioeconomic statusBreast Cancer Research and Treatment, 2010
- Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility geneNature Genetics, 2010
- Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American WomenJournal of Oncology, 2009
- Racial differences in the incidence of BRCA1 and BRCA2 mutations in a cohort of early onset breast cancer patients: African American compared to white womenJournal of Medical Genetics, 2005
- Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2Science, 2003
- The American Cancer Society Cancer Prevention Study II Nutrition CohortCancer, 2002