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. 2020 Dec 14;112(12):1213-1221.
doi: 10.1093/jnci/djaa040.

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

Julie R Palmer  1 , Eric C Polley  2 , Chunling Hu  2 , Esther M John  3 , Christopher Haiman  4 , Steven N Hart  2 , Mia Gaudet  5 , Tuya Pal  6 , Hoda Anton-Culver  7 , Amy Trentham-Dietz  8 , Leslie Bernstein  9 , Christine B Ambrosone  10 , Elisa V Bandera  11 , Kimberly A Bertrand  1 , Traci N Bethea  1 , Chi Gao  12 , Rohan D Gnanaolivu  2 , Hongyan Huang  12 , Kun Y Lee  2 , Loic LeMarchand  13 , Jie Na  2 , Dale P Sandler  14 , Payal D Shah  15 , Siddhartha Yadav  2 , William Yang  2 , Jeffrey N Weitzel  9 , Susan M Domchek  15 , David E Goldgar  1   6 , Katherine L Nathanson  15 , Peter Kraft  2 , Song Yao  2 , Fergus J Couch  2
Affiliations

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

Julie R Palmer et al. J Natl Cancer Inst. .

Erratum in

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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Figures

Figure 1.
Figure 1.
Prevalence of mutations in women with any breast cancer, estrogen receptor-negative (ER-neg) breast cancer, and ER-positive (ER-pos) breast cancer, according to age (in years) at diagnosis and first-degree family history (FHx) of breast cancer. *Any mutation indicates any pathogenic mutation in 12 known breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53).
Figure 2.
Figure 2.
Estimates of absolute risk of breast cancer through age 85 years in African American women who are carriers of pathogenic mutations in 4 specific genes. Dotted line in each figure represents absolute risk of US population of African American women regardless of carrier status.
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Comment in

References

    1. Easton DF, Pharoah PD, Antoniou AC, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372(23):2243–2257. - PMC - PubMed
    1. Couch FJ, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190–1196. - PMC - PubMed
    1. King MC, Marks JH, Mandell JB, et al. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302(5645):643–646. - PubMed
    1. Goldgar DEBCFRHealey S, Dowty JG, et al. Rare variants in the ATM gene and risk of breast cancer. Breast Cancer Res. 2011;13(4):R73. - PMC - PubMed
    1. Renwick A, Thompson D, Seal S, et al. Breast Cancer Susceptibility Collaboration (UK). ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet. 2006;38(8):873–875. - PubMed

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