Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study

Abstract

<b>Background:</b> Single nucleotide polymorphisms (SNPs) affecting microRNA (miR) sequences may influencecarcinogenesis. Our current study primarily aimed to confirm previously conducted association studies betweenrs2910164 found on miR-146a, and rs11614913 located on miR-196a2 polymorphisms and cancer phenotypesin the Japanese elderly population. rs2910164 (G/C) and rs11614913 (T/C) polymorphisms were determined bygenotyping on the samples collected from 1,351 consecutive autopsy cases registered in the Japanese SNPs forgeriatric research (JG-SNP) data base. Cancer samples were systematically reviewed, pathologically verified andassessed with respect to miR-146a and miR-196a2 genotypic variation. The current study covered 726 males and625 females with a mean age of 80.3±8.9 years. The study included 524 subjects without cancer and 827 subjectswith at least one type of cancer, such as gastric (n=160), lung (n=148), colorectal (n=116) or others. Males withcancers (n=467) were more numerous than females (n=360). Both rs11614913 (CT: TT adjusted odds ratio (OR)95% confidence interval (95%CI)=0.98 (0.75-1.28), p=0.873, CC: TT adjusted OR (95%CI)=1.06 (0.76-1.47),p=0.737, CT+CC: TT, adjusted OR (95%CI)=0.99 (0.77-1.29), p=0.990), and rs2910164 (CG: CC adjusted OR(95%CI)=1.12 (0.87-1.44), p=0.383, GG: CC adjusted OR (95%CI)=1.03 (0.71-1.48), p=0.887, CG+GG: CCadjusted OR (95%CI)=1.10 (0.87-1.39), p=0.446) polymorphisms did not show significant association with overallcancer in all subjects. However, “CC” genotype in rs11614913 polymorphism was significantly associated withincreased gastric cancer (n=160) in all subjects (CC: CT+TT, adjusted OR (95%CI)=1.50 (1.02-2.22), p=0.040).We found that rs11614913 and rs2910164 do not pose general cancer risk, but rs11614913 may influence gastriccancer in Japanese elderly population. Confirmation of our study results requires further investigations withlarger subject populations.