Association Between MicroRNA196a2 rs11614913 Genotypes and the Risk of Non-Small Cell Lung Cancer in Korean Population
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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 rs11614913polymorphisms and NSCLC risk require confirmation through additional larger studies.
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 rs11614913polymorphisms and NSCLC risk require confirmation through additional larger studies.
참고문헌 (26)
- Lagos-Quintana M, "Identification of novel genes coding for small expressed RNAs", Science, 294(5543), pp.853~858 (2001)
- Lee RC, "An extensive class of small RNAs in Caenorhabditis elegans", Science, 294(5543), pp.862~864 (2001)
- Bartel DP, "MicroRNAs: genomics, biogenesis, mechanism, and function", Cell, 116(2), pp.281~297 (2004)
- Ambros V, "MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing", Cell, 113(6), pp.673~676 (2003)
- Lu J, "MicroRNA expression profiles classify human cancers", Nature, 435(7043), pp.834~838 (2005)
- Esquela-Kerscher A, "Oncomirs-microRNAs with a role in cancer", Nat Rev Cancer, 6(4), pp.259~269 (2006)
- Kumar MS, "Impaired microRNA processing enhances cellular transformation and tumorigenesis", Nat Genet, 39(5), pp.673~677 (2007)
- Takamizawa J, "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival", Cancer Res, 64(11), pp.3753~3756 (2004)
- Hayashita Y, "A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation", Cancer Res, 65(21), pp.9628~9632 (2005)
- Rinaldi A, "Concomitant MYC and microRNA cluster miR-17-92 (C13orf25) amplification in human mantle cell lymphoma", Leuk Lymphoma, 48(2), pp.410~412 (2007)
- Calin GA, "Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia", Proc Natl Acad Sci USA, 99(24), pp.15524~15529 (2002)
- Brueckner B, "The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function", Cancer Res, 67(4), pp.1419~1423 (2007)
- Lum AM, "Retroviral activation of the mir-106a microRNA Cistron in T lymphoma", Retrovirology, 4, pp.5~ (2007)
- Slape C, "Retroviral insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation", Cancer Res, 67(11), pp.5148~5155 (2007)
- Hu Z, "Genetic variants of miRNA sequences and non small cell lung cancer survival", J Clin Invest, 118(7), pp.2600~2608 (2008)
- Tian T, "A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese", Cancer Epidemiol Biomarkers Prev, 18(4), pp.1183~1187 (2009)
- Ruvkun G, "Molecular biology. Glimpses of a tiny RNA world", Science, 294(5543), pp.797~799 (2001)
- Thum T, "MicroRNAs: novel regulators in cardiac development and disease", Cardiovasc Res, 79(4), pp.562~570 (2008)
- van Rooij E, "A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure", Proc Natl Acad Sci USA, 103(48), pp.18255~18260 (2006)
- van Rooij E, "Control of stress-dependent cardiac growth and gene expression by a microRNA", Science, 316(5824), pp.575~579 (2007)
- Sayed D, "MicroRNAs play an essential role in the development of cardiac hypertrophy", Circ Res, 100(3), pp.416~424 (2007)
- Zhao Y, "Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2", Cell, 129(2), pp.303~317 (2007)
- Hoffman AE, "microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis", Cancer Res, 69(14), pp.5970~5977 (2009)
- Xu J, "Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population", Hum Mutat, 30(8), pp.1231~1236 (2009)
- Hu Z, "Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women", Hum Mutat, 30(1), pp.79~84 (2009)
- Zhou B, "Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy", Clin Chim Acta, 411(17), pp.1287~1290 (2010)
