Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study
Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study
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DOI：
10.7314/apjcp.2014.15.5.2101
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Arai, Tomio
中科院分区：
文献类型：
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作者：
Parlayan, Cuneyd;Ikeda, Shinobu;Arai, Tomio
背景：影响microRNA（miR）序列的单核苷酸多态性（SNPs）可能影响癌的发生。我们目前的研究主要旨在确认先前在日本老年人群中发现的miR-146 a上的rs 2910164和位于miR-196 a2多态性和癌症表型上的rs 11614913之间的关联研究。通过对从日本老年研究SNP（JG-SNP）数据库中登记的1，351例连续尸检病例收集的样本进行基因分型，确定rs 2910164（G/C）和rs 11614913（T/C）多态性。对癌症样本进行系统性审查，病理学验证和评估miR-146 a和miR-196 a2基因型变异。本研究涵盖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名未患癌症的受试者和827名至少患有一种癌症的受试者，如胃癌（n=160）、肺癌（n=148）、结直肠癌（n=116）或其他癌症。男性癌症患者（n=467）多于女性（n=360）。两个rs 11614913（CT：TT调整后的比值比（OR）95%置信区间（95%CI）=0.98（0.75-1.28），p=0.873，CC：TT校正OR（95%CI）=1.06（0.76-1.47），p=0.737，CT+CC：TT，校正OR（95%CI）=0.99（0.77-1.29），p=0.990）和rs 2910164（CG：CC校正OR（95%CI）=1.12（0.87-1.44），p=0.383，GG：CC校正OR（95%CI）=1.03（0.71-1.48），p=0.887，CG+GG：CC校正OR（95%CI）=1.10（0.87-1.39），p=0.446）多态性未显示与所有受试者的总体癌症显著相关。然而，在所有受试者中，rs 11614913多态性中的“CC”基因型与胃癌的增加（n=160）显著相关（CC：CT+TT，校正OR（95%CI）=1.50（1.02-2.22），p=0.040）。我们发现rs 11614913和rs 2910164不构成一般癌症风险，但rs 11614913可能影响日本老年人群的胃癌。我们的研究结果的确认需要更大的受试者人群的进一步研究。
Background: 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.