Breast Cancer Institute, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, 270 Dong'an Road, Shanghai 200032, People's Republic of China.
Breast Cancer Res Treat. 2012 May;133(1):111-6. doi: 10.1007/s10549-011-1700-2. Epub 2011 Aug 3.
Deleterious mutations in several genes that are involved in repair of damage to DNA have been associated with an increased risk of breast cancer. Recent studies have shown sequence variants in two such genes, RAD50 and NBS1, which can be predisposed to breast cancer. The aim of this study is to elucidate the contribution of RAD50 and NBS1 germline mutations to the etiology of non-BRCA1/2 hereditary breast cancer in China. We conducted a mutational analysis of RAD50 and NBS1 in genomic DNA from 384 Chinese women with early-onset breast cancer and/or affected relatives. All the coding exons and adjacent intronic splice junction rejoins of RAD50 and NBS1 were screened using PCR-DHPLC and DNA sequencing analysis. Among all cases, no obviously deleterious mutations were observed in RAD50; one synonymous change c.102G>A at codon 34 and one single nucleotide polymorphism IVS9 + 19C>T were identified in NBS1. Furthermore, there was no remarkable difference in the allele frequency of NBS1 c.553G>C (E185Q) between cases (172/384) and controls (182/420). Our results exclude the possible role of RAD50 and NBS1 in familial breast cancer predisposition in Chinese women, and there is no evidence for the recommendation of RAD50 and NBS1 for genetic testing in China.
几种参与 DNA 损伤修复的基因中的有害突变与乳腺癌风险增加有关。最近的研究表明，两个这样的基因 RAD50 和 NBS1 存在序列变异，可能导致乳腺癌易感性。本研究旨在阐明 RAD50 和 NBS1 种系突变在中国非 BRCA1/2 遗传性乳腺癌发病机制中的作用。我们对 384 名早发性乳腺癌和/或受影响亲属的中国女性的 RAD50 和 NBS1 基因组 DNA 进行了突变分析。使用 PCR-DHPLC 和 DNA 测序分析筛选 RAD50 和 NBS1 的所有编码外显子和相邻内含子剪接接头连接。在所有病例中，RAD50 未观察到明显的有害突变；在 NBS1 中鉴定出一个同义变化 c.102G>A 在密码子 34 处和一个单核苷酸多态性 IVS9 + 19C>T。此外，NBS1 c.553G>C（E185Q）的等位基因频率在病例（172/384）和对照组（182/420）之间没有显著差异。我们的结果排除了 RAD50 和 NBS1 在中国人中家族性乳腺癌易感性中的可能作用，并且没有证据表明 RAD50 和 NBS1 在中国进行基因检测的推荐。
