A genetic variant in MiR-146a modifies digestive system cancer risk: a meta-analysis.

MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83- 0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations.

[1]  J. Ioannidis,et al.  Quantitative Synthesis in Systematic Reviews , 1997, Annals of Internal Medicine.

[2]  R. Russell,et al.  bantam Encodes a Developmentally Regulated microRNA that Controls Cell Proliferation and Regulates the Proapoptotic Gene hid in Drosophila , 2003, Cell.

[3]  V. Ambros The functions of animal microRNAs , 2004, Nature.

[4]  Ammarin Thakkinstian,et al.  A method for meta‐analysis of molecular association studies , 2005, Statistics in medicine.

[5]  A. Sutton,et al.  Comparison of two methods to detect publication bias in meta-analysis. , 2006, JAMA.

[6]  M. Moraga,et al.  ATM allelic variants associated to hereditary breast cancer in 94 Chilean women: susceptibility or ethnic influences? , 2007, Breast Cancer Research and Treatment.

[7]  Barbara Jarzab,et al.  Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma , 2008, Proceedings of the National Academy of Sciences.

[8]  Hua Zhao,et al.  A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. , 2008, Carcinogenesis.

[9]  B. Shastry SNPs: impact on gene function and phenotype. , 2009, Methods in molecular biology.

[10]  Xiaoguang Fang,et al.  MicroRNAs: novel regulators in the hallmarks of human cancer. , 2009, Cancer letters.

[11]  Y. Tomari,et al.  The microRNA pathway and cancer , 2010, Cancer science.

[12]  B. Mittal,et al.  Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population , 2010, Journal of Human Genetics.

[13]  Bin Wang,et al.  Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. , 2010, World journal of gastroenterology.

[14]  Weibo Liang,et al.  The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis , 2010, Journal of experimental & clinical cancer research : CR.

[15]  Gang Xiong,et al.  A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han , 2010, Familial Cancer.

[16]  T. Tahara,et al.  Association Between Common Genetic Variants in Pre‐microRNAs and Gastric Cancer Risk in Japanese Population , 2010, Helicobacter.

[17]  David Baltimore,et al.  Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses , 2010, Cell.

[18]  D. Dick Gene-environment interaction in psychological traits and disorders. , 2011, Annual review of clinical psychology.

[19]  M. Albitar,et al.  Circulating MicroRNAs as Biomarkers for Hepatocellular Carcinoma , 2011, Journal of clinical gastroenterology.

[20]  D. Heo,et al.  MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma , 2011, Clinical Cancer Research.

[21]  S. Ambs,et al.  Interactions among genes, tumor biology and the environment in cancer health disparities: examining the evidence on a national and global scale. , 2011, Carcinogenesis.

[22]  N. Kim,et al.  Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population. , 2012, Gene.

[23]  A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population , 2013, Archives of Toxicology.

[24]  F. Lammert,et al.  A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort. , 2012, Hepatobiliary & pancreatic diseases international : HBPD INT.

[25]  Baosen Zhou,et al.  Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis , 2013, Molecular Biology Reports.

[26]  Mu-Kuan Chen,et al.  Impacts of MicroRNA Gene Polymorphisms on the Susceptibility of Environmental Factors Leading to Carcinogenesis in Oral Cancer , 2012, PloS one.

[27]  R. Vyzula,et al.  Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer. , 2012, World journal of gastroenterology.

[28]  Yan Zhou,et al.  A functional polymorphism in Pre-miR-146a is associated with susceptibility to gastric cancer in a Chinese population. , 2012, DNA and cell biology.

[29]  Federica Gemignani,et al.  Role of variations within microRNA-binding sites in cancer. , 2012, Mutagenesis.

[30]  Jingdong Xie,et al.  Three common functional polymorphisms in microRNA encoding genes in the susceptibility to hepatocellular carcinoma: a systematic review and meta-analysis. , 2013, Gene.

[31]  K. Kwack,et al.  Association of the miR‐146aC>G, miR‐149T>C, miR‐196a2T>C, and miR‐499A>G polymorphisms with gastric cancer risk and survival in the korean population , 2013, Molecular carcinogenesis.

[32]  M. Gazouli,et al.  MicroRNA gene polymorphisms in pancreatic cancer. , 2013, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[33]  Charles E. Vejnar,et al.  Human polymorphism at microRNAs and microRNA target sites. , 2013 .

[34]  X. Su,et al.  Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population , 2013, Journal of Cancer Research and Clinical Oncology.

[35]  Fan Wang,et al.  The miR-146a rs2910164 G > C polymorphism and susceptibility to digestive cancer in Chinese. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[36]  H. Gu,et al.  MiR-196a2 rs11614913 T > C polymorphism and risk of esophageal cancer in a Chinese population. , 2013, Human immunology.

[37]  R. Vatsyayan,et al.  Nutlin‐3 enhances sorafenib efficacy in renal cell carcinoma , 2013, Molecular carcinogenesis.