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.

中文翻译：

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种系易感基因突变对非裔美国女性乳腺癌风险的贡献。

背景 与乳腺癌易感基因遗传突变相关的非裔美国人 (AA) 女性患乳腺癌的风险尚未明确定义。因此，多基因种系遗传性癌症检测试剂盒是否适用于该人群尚不清楚。我们评估了来自 10 项流行病学研究的 5054 名患有乳腺癌的 AA 女性和 4993 名未受影响的 AA 女性的基于面板的基因突变与乳腺癌风险之间的关联。方法 使用 QIAseq 多重扩增子组对种系 DNA 样本进行 23 种癌症易感基因突变的测序。通过调整研究设计、年龄和乳腺癌家族史，估计与乳腺癌风险相关的突变发生率和比值比 (OR)。结果 在 10 个中鉴定出致病突变。3% 的雌激素受体 (ER) 阴性乳腺癌女性、5.2% 的 ER 阳性乳腺癌女性和 2.3% 的未受影响女性。BRCA1、BRCA2 和 PALB2 的突变与乳腺癌的高风险相关（OR = 47.55，95% 置信区间 [CI] = 10.43 至 >100；OR = 7.25，95% CI = 4.07 至 14.12；OR = 8.54， 95% CI = 3.67 至 24.95）。RAD51D 突变与 ER 阴性疾病的高风险相关（OR = 7.82，95% CI = 1.61 至 57.42）。对于 ER 阳性癌症的 CHEK2、ATM、ERCC3 和 FANCC 突变以及所有乳腺癌的 RECQL 突变，观察到中等风险。结论 该研究确定了 AA 人群中易患乳腺癌的基因，证明了当前用于 AA 女性的乳腺癌检测组的有效性，