Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers
Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers
复制标题
RAD51D 种系突变与 BRCA1/2 阴性乳腺癌的乳腺癌风险和生存之间的关联
DOI：
10.1093/annonc/mdy338
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发表时间：
2018-10-01
影响因子：
50.5
通讯作者：
Xie, Y.
中科院分区：
文献类型：
--
作者：
Chen, X.;Li, Y.;Xie, Y.
背景
RAD51D通过同源重组参与DNA双链断裂修复，在维持基因组稳定性中发挥重要作用。 RAD51D 种系突变与乳腺癌风险和生存之间的关联尚未完全阐明。
患者和方法
使用多基因面板在 7657 名未选择的 BRCA1/2 种系突变阴性乳腺癌患者中确定了 RAD51D 种系突变。通过桑格测序在 7947 名健康对照中筛选出 RAD51D 复发突变 p.K91fs。
结果
在这 7657 名未经选择的乳腺癌患者队列中，共有 29 例（0.38%）携带有害的 RAD51D 种系突变。在这 7657 名患者中，有 18 例 (0.24%) 被鉴定出 RAD51D 复发突变 p.K91fs。相比之下，7947 名健康对照中的 8 名发现了 p.K91fs 突变，频率为 0.10%。 RAD51D p.K91fs 突变与未选择的乳腺癌中乳腺癌风险增加显着相关 [比值比 = 2.34，95% 置信区间 (CI) 1.02-5.38； P = 0.040]。 RAD51D突变携带者比非携带者诊断时年龄更小（P = 0.006），并且更有可能患三阴性乳腺癌（P = 0.003）、雌激素受体阴性（P = 0.005）和高级别癌症（P = 0.023）。此外，RAD51D 突变携带者的无复发生存率明显较差[未调整的风险比 (HR) = 3.00，95% CI 1.56-5.80； P = 0.001] 和远处无复发生存率（未调整 HR = 2.54，95% CI 1.14-5.67；P = 0.023）均高于非携带者。
结论
RAD51D 复发突变 p.K91fs 会导致乳腺癌风险适度增加，并且与非携带者相比，RAD51D 突变携带者的生存率较差。
Background
RAD51D is involved in DNA double-strand break repair by homologous recombination and plays an important role in the maintenance of genomic stability. The associations between RAD51D germline mutations and breast cancer risk and survival are not fully elucidated.
Patients and methods
RAD51D germline mutations were determined using a multigene panel in 7657 unselected breast cancer patients who were negative for BRCA1/2 germline mutations. The RAD51D recurrent mutation p.K91fs was screened in 7947 healthy controls by Sanger sequencing.
Results
A total of 29 cases (0.38%) carried deleterious RAD51D germline mutations among this cohort of 7657 unselected breast cancer patients. The RAD51D recurrent mutation p.K91fs was identified in 18 cases (0.24%) of these 7657 patients. In contrast, the p.K91fs mutation was found in 8 of 7947 healthy controls with a frequency of 0.10%. The RAD51D p.K91fs mutation was significantly associated with increased breast cancer risk in unselected breast cancer [odds ratio = 2.34, 95% confidence interval (CI) 1.02-5.38; P = 0.040]. RAD51D mutation carriers were diagnosed at a younger age (P = 0.006) and were more likely to be triple-negative breast cancer (P = 0.003), estrogen receptor negative (P = 0.005) and high-grade cancers (P = 0.023) than noncarriers. Furthermore, RAD51D mutation carriers had a significantly worse recurrence-free survival [unadjusted hazard ratio (HR) = 3.00, 95% CI 1.56-5.80; P = 0.001] and distant recurrence-free survival (unadjusted HR = 2.54, 95% CI 1.14-5.67; P = 0.023) than noncarriers.
Conclusion
The RAD51D recurrent mutation, p.K91fs, confers a moderately increased breast cancer risk, and RAD51D mutation carriers have an unfavorable survival compared with noncarriers.