Abstract 1488: Association between microrna binding site polymorphism and susceptibility to colorectal cancer in Korean population

Abstract

Abstract Background : MicroRNAs (miRNAs) play an important role in the colorectal cancer tumorigenesis by regulation of gene expression through binding to 3′ untranslational region (UTR) of target gene. Single nucleotide polymorphism (SNP) within 3′UTR of gene could be affected by miRNA binding. Docking protein 3 (DOK3) is adapter protein that acts as tumor suppressor through modulating tyrosine kinase signaling. Methods : One hundred thirty five SNPs were selected in Silico analysis for the current study from 3′UTR SNPs of SNP database, which was based on several miRNA database, calculating miRNA bind efficiency on polymorphism, and HapMap database. Here independent two set of study was designed, 380 healthy controls and 371 colorectal adenocarcinoma patients were enrolled in discovery set, and 524 healthy controls and 521 colorectal adenocarcinoma patients were enrolled in replication set. The SNP genotyping was performed using the Sequenom MassARRAY Result: In discovery set, 16 SNPs were significantly associated with colorectal cancer in any genetic model from 135 SNP genotyping. Among 16 SNPs, DOK3 rs2279398G>A was significantly associated in replication set recessive model (adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.44-0.97, P = 0.03). In combined analysis, DOK3 rs2279398G>A was associated with significantly decreased risk of colorectal cancer in codominant and recessive model (adjusted OR = 0.84, 95% CI = 0.73-0.96, P = 0.012, adjusted OR = 0.65, CI = 0.49-0.88, P = 0.004, respectively). Conclusion : DOK3 rs2279398G>A may affect the expression of DOK3 by altering miRNA binding efficiency on miRNA-binding sites of the 3′-UTR of DOK3 and impact on colorectal cancer tumorigenesis. This finding suggests that DOK3 rs2279398G>A may be a useful biomarker for determining the susceptibility to colorectal cancer. Citation Format: Byung Woog Kang, Hyosung Jeon, Yee Soo Chae, Soo Jung Lee, Jong Gwang Kim, Hyunchul Lee, Eun-Jin Lee, Myung Hoon Lee, Jae Yong Park, Gyu Seog Choi, Jun Seok Park. Association between microrna binding site polymorphism and susceptibility to colorectal cancer in Korean population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1488. doi:10.1158/1538-7445.AM2014-1488