Wang Keren, Ye Yuqin, Xu Zheli, Zhang Xuan, Hou Zhifu, Cui Youbin, Song Yan
China Japan Union Hospital of Jilin University, Changchun, PR China.
Cancer Genet Cytogenet. 2010 Jul 1;200(1):40-6. doi: 10.1016/j.cancergencyto.2010.03.006.
The etiology of breast cancer is associated with several factors, the most important being genetic susceptibility. Both BRCA1/2 and ATM/ATR play a role in DNA repair pathways and breast cancer. The aims of our investigation were to confirm the contributions of the known polymorphisms in these genes and investigate the pattern of their interaction. A total of 360 Han Chinese blood samples were collected from 180 patients with breast cancer and 180 healthy controls. In total, five single-nucleotide polymorphisms (SNP) in these genes were genotyped using polymerase chain reaction-based restriction fragment length polymorphism analysis. Combined effects of paired SNP were tested by the Multifactor Dimensionality Reduction (MDR) method and theory of Information Gain (IG). By MDR analysis, the best model was determined to be a five-locus site model. Interaction tree by the hierarchical clustering method showed that the ATR mutant rs13091637 gave a maximum stand-alone IG value, while the ATM mutant rs611646 showed the lowest IG value but had the top interaction effect. These results suggest that combined effects of the polymorphisms in these genes may confer susceptibility to breast cancer in a Chinese Han cohort (n = 360). Each of the variants, though, performs a different role in the pathogenetic mechanism of breast cancer.
乳腺癌的病因与多种因素相关，其中最重要的是遗传易感性。BRCA1/2和ATM/ATR在DNA修复途径及乳腺癌中均发挥作用。我们研究的目的是确认这些基因中已知多态性的作用，并探究它们的相互作用模式。共采集了180例乳腺癌患者和180例健康对照的360份汉族血液样本。使用基于聚合酶链反应的限制性片段长度多态性分析对这些基因中的5个单核苷酸多态性（SNP）进行基因分型。通过多因素降维法（MDR）和信息增益理论（IG）检测配对SNP的联合效应。通过MDR分析，确定最佳模型为五位点模型。采用层次聚类法构建的相互作用树显示，ATR突变体rs13091637的独立IG值最高，而ATM突变体rs611646的IG值最低，但具有最强的相互作用效应。这些结果表明，这些基因多态性的联合效应可能使中国汉族人群（n = 360）易患乳腺癌。不过，每个变体在乳腺癌发病机制中发挥着不同作用。
