Genome-wide association study identifies possible genetic risk factors for colorectal adenomas.

BACKGROUND Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. METHODS In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. RESULTS No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)). CONCLUSIONS This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. IMPACT These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.