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Association between microRNA196a2 rs11614913 genotypes and the risk of non-small cell lung cancer in Korean population.

ABSTRACT: OBJECTIVES: The microRNA (miRNA) miR-196a2 may play an important role in lung cancer development and survival by altering binding activity of target mRNA. In this study, we evaluated their associations with the susceptibility of non-small cell lung cancers (NSCLC) by case-control study in a Korean population. METHODS: We performed genotyping analyses for miR-196a2 rs11614913 T/C at miRNA regions in a case-control study using blood samples of 406 NSCLC patient and 428 cancer-free control groups. RESULTS: The total C allele frequencies for miR-196a2 were 48.8% for the patients and 45.6% for the controls; and the genotype frequencies of TT, TC, and CC were 23.7%, 55.2%, and 21.1% for the patients and 31.1%, 46.35%, and 22.4% for the controls (p<0.05). Participants who possesses TC/CC genotypes showed high risk for NSCLC compared to those possessed TT genotypes (OR, 1.42; 95% CI, 1.03 to 1.96). The association was persisted in 60 and older age group, male, smokers, those without family history for cancer. However, no significant association of CC genotypes in recessive genetic model was observed. CONCLUSIONS: In conclusion, this case-control study provides evidence that miR-196a2 rs11614913 C/T polymorphisms are associated with a significantly increased risk of NSCLC in a dominant model, indicating that common genetic polymorphisms in miR-196a2 rs11614913 are associated with NSCLC. The association of miR196a2 rs11614913 polymorphisms and NSCLC risk require confirmation through additional larger studies.

SUBMITTER: Hong YS

PROVIDER: S-EPMC3249248 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Association between microRNA196a2 rs11614913 genotypes and the risk of non-small cell lung cancer in Korean population.

Hong Young-Seoub YS Kang Ho-Jin HJ Kwak Jong-Young JY Park Byung Lae BL You Chang-Hun CH Kim Yu-Mi YM Kim Heon H

Journal of preventive medicine and public health = Yebang Uihakhoe chi 20110501 3

<h4>Objectives</h4>The microRNA (miRNA) miR-196a2 may play an important role in lung cancer development and survival by altering binding activity of target mRNA. In this study, we evaluated their associations with the susceptibility of non-small cell lung cancers (NSCLC) by case-control study in a Korean population.<h4>Methods</h4>We performed genotyping analyses for miR-196a2 rs11614913 T/C at miRNA regions in a case-control study using blood samples of 406 NSCLC patient and 428 cancer-free con ...[more]

PMID: 21617338

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Project description:Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P=0.023]. In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed.

Dataset Information

Association between microRNA196a2 rs11614913 genotypes and the risk of non-small cell lung cancer in Korean population.

Publications

Association between microRNA196a2 rs11614913 genotypes and the risk of non-small cell lung cancer in Korean population.

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