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日本老年人中miR-146a和miR-196a2单核苷酸多态性与癌症患病率的关联分析:一项病例对照研究

Association analysis of single nucleotide polymorphisms in miR-146a and miR-196a2 on the prevalence of cancer in elderly Japanese: a case-control study.

作者信息

Parlayan Cuneyd, Ikeda Shinobu, Sato Noriko, Sawabe Motoji, Muramatsu Masaaki, Arai Tomio

机构信息

Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(5):2101-7. doi: 10.7314/apjcp.2014.15.5.2101.

DOI:10.7314/apjcp.2014.15.5.2101
PMID:24716941
Abstract

Single nucleotide polymorphisms (SNPs) affecting microRNA (miR) sequences may influence carcinogenesis. Our current study primarily aimed to confirm previously conducted association studies between rs2910164 found on miR-146a, and rs11614913 located on miR-196a2 polymorphisms and cancer phenotypes in the Japanese elderly population. rs2910164 (G/C) and rs11614913 (T/C) polymorphisms were determined by genotyping on the samples collected from 1,351 consecutive autopsy cases registered in the Japanese SNPs for geriatric research (JG-SNP) data base. Cancer samples were systematically reviewed, pathologically verified and assessed with respect to miR-146a and miR-196a2 genotypic variation. The current study covered 726 males and 625 females with a mean age of 80.3±8.9 years. The study included 524 subjects without cancer and 827 subjects with at least one type of cancer, such as gastric (n=160), lung (n=148), colorectal (n=116) or others. Males with cancers (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: CC adjusted OR (95%CI)=1.10 (0.87-1.39), p=0.446) polymorphisms did not show significant association with overall cancer in all subjects. However, "CC" genotype in rs11614913 polymorphism was significantly associated with increased 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 gastric cancer in Japanese elderly population. Confirmation of our study results requires further investigations with larger subject populations.

摘要

影响微小RNA(miR)序列的单核苷酸多态性(SNP)可能会影响癌症发生。我们当前的研究主要旨在证实先前在日本老年人群中进行的关于miR - 146a上的rs2910164以及miR - 196a2多态性位点rs11614913与癌症表型之间的关联研究。通过对从日本老年研究单核苷酸多态性(JG - SNP)数据库中登记的1351例连续尸检病例采集的样本进行基因分型,确定了rs2910164(G/C)和rs11614913(T/C)多态性。对癌症样本进行了系统回顾、病理验证,并评估了miR - 146a和miR - 196a2的基因型变异。本研究涵盖了726名男性和625名女性,平均年龄为80.3±8.9岁。该研究包括524名无癌症的受试者和827名患有至少一种癌症的受试者,如胃癌(n = 160)、肺癌(n = 148)、结直肠癌(n = 116)或其他癌症。患癌男性(n = 467)比女性(n = 360)多。rs11614913(CT: TT调整优势比(OR)95%置信区间(95%CI)= 0.98(0.75 - 1.28),p = 0.873;CC: TT调整OR(95%CI)= 1.06(0.76 - 1.47),p = 0.737;CT + CC: TT调整OR(95%CI)= 0.99(0.77 - 1.29))和rs2910164(CG: CC调整OR(95%CI)= 1.12(0.87 - 1.44),p = 0.383;GG: CC调整OR(95%CI)= 1.03(0.71 - 1.48),p = 0.887;CG + GG: CC调整OR(95%CI)= 1.10(0.87 - 1.39),p = 0.446)多态性在所有受试者中与总体癌症均未显示出显著关联。然而,rs11614913多态性中的“CC”基因型在所有受试者中与胃癌(n = 160)增加显著相关(CC: CT + TT调整OR(95%CI)= 1.50(1.02 - 2.22),p = 0.040)。我们发现rs11614913和rs2910164不会构成一般癌症风险,但rs11614913可能会影响日本老年人群中的胃癌。我们研究结果的确认需要对更大的受试者群体进行进一步调查。

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