Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women
Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women
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DOI：
10.1093/jnci/djaa040
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发表时间：
2020-12-01
影响因子：
10.3
通讯作者：
Couch, Fergus J.
中科院分区：
文献类型：
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作者：
Palmer, Julie R.;Polley, Eric C.;Couch, Fergus J.
背景资料：与乳腺癌易感基因遗传突变相关的非裔美国人（AA）妇女患乳腺癌的风险尚未明确。因此，多基因生殖系遗传性癌症检测板是否适用于这一人群尚不清楚。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女性中基于小组的基因突变与乳腺癌风险之间的关联。方法：使用QIAseq多重扩增子面板对23个癌症易感基因中的突变进行种系DNA样本测序。通过调整研究设计、年龄和乳腺癌家族史，估计突变的患病率和与乳腺癌风险相关的比值比（OR）。结果如下：在10.3%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%的未受影响女性中发现了致病性突变。BRCA 1、BRCA 2和PALB 2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）。RAD 51 D突变与ER阴性疾病的高风险相关（OR = 7.82，95%CI = 1.61至57.42）。CHEK 2，ATM，ERCC 3和FANCC突变与ER阳性癌症以及RECQL突变与所有乳腺癌的风险均为中等。结论：该研究确定了AA人群中易患乳腺癌的基因，证明了目前乳腺癌检测面板用于AA女性的有效性，并为增加AA患者的癌症基因检测提供了基础。
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.