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.
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