rs10795668 located at 10p14 is associated with colorectal cancer risk in Han Chinese

Abstract

BACKGROUND: Colorectal cancer (CRC) is the second commonest cancer in Hong Kong. While high-penetrance germline mutations account for <6% of cases, much of the remaining variation in genetic risk (30%) may be attributable to multiple low-penetrance variants. Previous genome-wide association studies (GWAS) have identified a number of CRC susceptibility alleles in the Caucasian population. Our study investigated the association of 13 previously reported SNPs with CRC risk in the Han Chinese population in Hong Kong. METHOD: Genomic DNA samples from 1,440 Chinese subjects were genotyped using the Sequenom Mass ARRAY system. Association analysis was successfully performed on 714 cases (male = 444; female = 270) and 717 controls (male = 442; female = 275) with an overall genotyping call rate of 99.87%. PLINK was used for quality-control testing and data analysis. Allelic frequencies were compared by chi-squared tests and one-tailed p-values were corrected for multiple testing using Bonferroni and False Discovery Rate (FDR). RESULTS: One SNP, rs10795668 located at 10p14, was found to be significantly associated with CRC (Bonferroni corrected p = 0.016), with effect size similar to Caucasian data (OR = 0.79, 95% CI 0.68-0.92). Using a FDR of 0.1, four additional SNPs (rs4779584, rs12953717, rs7014346 and rs4939827) were also found to be significant. Q-Q plot showed that all 13 p-values were more significant than the expectations for their ranks, under the null hypothesis of a uniform distribution of p-values. CONCLUSION: Our study shows that rs10795668 is associated with CRC risk in Hong Kong Han Chinese. Inadequate sample size may have led to under-estimation of the number of SNPs that are truly associated with CRC risk in our population. This result corroborates with previous findings in the Caucasian population.