Author's response to reviews Title: Genetic polymorphisms of DNA double strand break gene Ku70 and gastric cancer in Taiwan Authors: Mei-Due

I would like to thank you and the reviewers for the time and effort in reviewing our manuscript titled "Genetic polymorphisms of DNA double strand break gene Ku70 and gastric cancer in Taiwan" (MS:1098878852450640). We appreciate the constructive comments and suggestions that help improve our manuscript. We have addressed all the critiques raised by you and the reviewers. The point-by-point answers to each issue are provided below. Comments to the Author In this manuscript entitled " Genetic polymorphisms of DNA double strand break gene Ku70 and gastric cancer in Taiwan " , the authors performed an association study by comparing allele and genotype frequencies at three promoter and one intronic SNPs in a major candidate gene involved in DNA double strand break repair, Ku70, between 136 gastric cancer patients and 560 controls in Taiwan. They report significant associations between Ku70 promoter T-991C allele and genotype and risk to gastric cancer, whereas no differences in other Ku70 genotype or allele frequencies between patients and controls. The study is solid with a convincing hypothesis to carry out a candidate gene approach, a low-throughput but accurate genotyping method, and a standard statistical genetic analysis. The results will potentially contribute to our understanding of the role of Ku70 gene in gastric cancer. Additional LD analysis using their own data and ones available in HapMap database, and more careful interpretation will strengthen the manuscript. Major Comments 1. It would be critical to include a LD plot showing correlations among the three promoter SNPs and one intronic SNP in Ku70, which may explain as to why only-991 SNP but not the others shows associations. Answer: We have performed the LD analysis using our own data via the software of Hapmap. The results are shown as below. Obviously, the Ku70 promoter T-991C (rs5751129) may belong to different blocks as other three SNPs we investigated in this study in the population. This may help us to explain that only the Ku70 promoter T-991C (rs5751129) was significantly associated with gastric cancer, while the other three SNPs, promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron3 (rs132774) polymorphisms were not. 2. To support for their interpretation that " There may also be LD between Ku70 promoter T-991C polymorphism and other SNPs in exons, resulting in functional polymorphism and predisposing to gastric carcinogenesis', the authors should have made an attempt to analyze HapMap data, preferably from Asian individuals, showing that there is …