title: Association study of two inflammation-related polymorphisms with susceptibility to hepatocellular carcinoma: a meta-analysis.
abstract: BACKGROUND
  Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship.
  
  
  METHODS
  Meta-analysis was performed on the associations between the miR-146a rs2910164 C > G and miR-499 rs3746444 T > C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study.
  
  
  RESULTS
  Results show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR = 1.153, 95% CI 1.083-1.228, P < 0.001; GC versus CC: OR = 1.165, 95% CI 1.054-1.286, P = 0.003; GG versus CC: OR = 1.361, 95% CI 1.192-1.553, P < 0.001; GG/GC versus CC: OR = 1.213, 95% CI 1.104-1.333, P < 0.001; GG versus GC/CC: OR = 1.210, 95% CI 1.080-1.356, P < 0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR = 2.171, 95% CI = 1.149-4.104, P = 0.017) than those with TT genotype.
  
  
  CONCLUSIONS
  We conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.
authors.forename: Jiajing
authors.initials: J
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Xie
authors.forename: Shuilian
authors.initials: S
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
mesh_terms: D000818:Animals; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014422:Turkeys
chemical_list: C542542:MIRN146 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs
references.citation: PLoS One. 2012;7(6):e40039
references.pmid: 22768213
references.citation: DNA Cell Biol. 2012 Apr;31(4):524-30
references.pmid: 21861697
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Adv Exp Med Biol. 2013;774:1-20
references.pmid: 23377965
references.citation: Carcinogenesis. 2008 Nov;29(11):2126-31
references.pmid: 18711148
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: PLoS One. 2011;6(5):e20471
references.pmid: 21637771
references.citation: Nature. 2004 Sep 16;431(7006):350-5
references.pmid: 15372042
references.citation: Mol Biol Rep. 2012 Jun;39(6):7019-23
references.pmid: 22311030
references.citation: J Clin Invest. 2008 Jul;118(7):2600-8
references.pmid: 18521189
references.citation: Hum Mol Genet. 2007 May 1;16(9):1124-31
references.pmid: 17400653
references.citation: RNA. 2003 Jan;9(1):112-23
references.pmid: 12554881
references.citation: J Natl Cancer Inst. 1959 Apr;22(4):719-48
references.pmid: 13655060
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Ann Intern Med. 1997 Nov 1;127(9):820-6
references.pmid: 9382404
references.citation: Nat Med. 2011 Jan;17(1):71-8
references.pmid: 21186368
references.citation: Gene. 2011 Oct 15;486(1-2):104-9
references.pmid: 21807077
references.citation: Mol Biol Rep. 2013 Apr;40(4):3003-13
references.pmid: 23292097
references.citation: Neurosci Lett. 2012 Jul 11;521(1):71-5
references.pmid: 22659075
references.citation: Korean J Hepatol. 2007 Dec;13(4):530-42
references.pmid: 18159151
references.citation: Cancer Lett. 2009 Nov 28;285(2):116-26
references.pmid: 19464788
references.citation: Cytokine. 2011 Dec;56(3):695-8
references.pmid: 21978540
references.citation: Mol Biol Rep. 2012 Apr;39(4):4571-9
references.pmid: 21947843
references.citation: Gastroenterology. 2012 Jun;142(7):1431-43
references.pmid: 22504185
references.citation: Gene. 2013 Sep 25;527(2):584-93
references.pmid: 23791656
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7269-74
references.pmid: 18474871
references.citation: Mol Carcinog. 2013 Nov;52 Suppl 1:E28-38
references.pmid: 22711332
references.citation: Biochim Biophys Acta. 2009 Apr;1792(4):341-52
references.pmid: 19419692
references.citation: Scand J Gastroenterol. 2013 Jun;48(6):729-35
references.pmid: 23556482
references.citation: Methods Mol Biol. 2009;578:3-22
references.pmid: 19768584
references.citation: J Natl Cancer Inst. 2012 Dec 5;104(23):1808-14
references.pmid: 23197492
references.citation: Zhonghua Yu Fang Yi Xue Za Zhi. 2011 Mar;45(3):239-43
references.pmid: 21624236
references.citation: Gene. 2012 Aug 1;504(1):92-7
references.pmid: 22583825
references.citation: Cell. 2005 Jul 15;122(1):6-7
references.pmid: 16009126
references.citation: J Gastroenterol Hepatol. 2009 Mar;24(3):346-53
references.pmid: 19220670
references.citation: Gene. 2012 Oct 15;508(1):9-14
references.pmid: 22903035
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Breast Cancer Res Treat. 2011 Jan;125(2):571-4
references.pmid: 20640596
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Mutagenesis. 2012 Nov;27(6):779-88
references.pmid: 22952151
references.citation: Gene. 2012 Nov 10;509(2):267-72
references.pmid: 22922391
references.citation: PLoS One. 2012;7(9):e45042
references.pmid: 22970328