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Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis

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Abstract

MicroRNAs (miRNAs) are a class of new non-coding RNA, which may play a more important role in the pathogenesis of human cancers. Rs2910164 in miR-146a and rs3746444 in miR-499 are shown to be associated with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. We retrieved the relevant articles from PubMed databases. Studies were selected using specific inclusion and exclusion criteria. ORs and 95% CIs were calculated to access the strength of association between microRNA polymorphism and cancer risk. All analyses were performed using the Stata software. Twenty-nine studies were included in this meta-analysis. There were not significant associations between miR-146a rs2910164 and miR-499 rs3746444 polymorphisms with overall cancer risk. In the subgroup analysis by ethnicity, significantly affected cancer risks were found among Asians for both rs2910164 (GC vs. GG: OR = 0.89, 95% CI = 0.82–0.96; CC vs. GG: OR = 0.80, 95% CI = 0.66–0.97; GC + CC vs. GG: OR = 0.86, 95% CI = 0.76–0.97; C vs. G: OR = 0.91, 95% CI = 0.82–1.00) and rs3746444 (GG + AG vs. AA: OR = 1.21, 95% CI = 1.00–1.46). In the tumor type subgroup analysis, rs2910164 C allele decreased the risk of hepatocellular carcinoma (C vs. G: OR = 0.89, 95% CI = 0.80–1.00) and cervical squamous cell carcinoma (C vs. G: OR = 0.72, 95% CI = 0.62–0.84). The rs2910164 in miR-146a and the rs3746444 in miR-499 are likely to be associated with cancer risk.

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References

  1. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115:787–798

    Article  PubMed  CAS  Google Scholar 

  2. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10:94–108

    Google Scholar 

  3. Bartel DP, Chen CZ (2004) Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 5:396–400

    Article  PubMed  CAS  Google Scholar 

  4. Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12

    Article  PubMed  CAS  Google Scholar 

  5. Saunders MA, Liang H, Li WH (2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA 104:3300–3305

    Article  PubMed  CAS  Google Scholar 

  6. Chen K, Song F, Calin GA, Wei Q, Hao X, Zhang W (2008) Polymorphisms in microRNA targets: a gold mine for molecular epidemiology. Carcinogenesis 29:1306–1311

    Article  PubMed  CAS  Google Scholar 

  7. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274

    Article  PubMed  CAS  Google Scholar 

  8. Zhou B, Wang K, Wang Y, Xi M, Zhang Z, Song Y, Zhang L (2011) Common genetic polymorphisms in pre-microRNAs and risk of cervical squamous cell carcinoma. Mol Carcinog 50:499–505

    Article  PubMed  CAS  Google Scholar 

  9. Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H (2009) Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30:79–84

    Article  PubMed  CAS  Google Scholar 

  10. Yang H, Dinney CP, Ye Y, Zhu Y, Grossman HB, Wu X (2008) Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer. Cancer Res 68:2530–2537

    Article  PubMed  CAS  Google Scholar 

  11. Horikawa Y, Wood CG, Yang H, Zhao H, Ye Y, Gu J, Lin J, Habuchi T, Wu X (2008) Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Clin Cancer Res 14:7956–7962

    Article  PubMed  CAS  Google Scholar 

  12. Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H, Chen Y, Shen H (2009) A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 18:1183–1187

    Article  PubMed  CAS  Google Scholar 

  13. Srivastava K, Srivastava A, Mittal B (2010) Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population. J Hum Genet 55:495–499

    Article  PubMed  CAS  Google Scholar 

  14. Qiu LX, He J, Wang MY et al (2011) The association between common genetic variant of microRNA-146a and cancer susceptibility. Cytokine 56:695–698

    Article  PubMed  CAS  Google Scholar 

  15. Wang J, Bi J, Liu X, Li K, Di J, Wang B (2012) Has-miR-146a polymorphism (rs2910164) and cancer risk: a meta-analysis of 19 case–control studies. Mol Biol Rep 39:4571–4579

    Article  PubMed  CAS  Google Scholar 

  16. Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, Qian Y, Zhao W, Wu J (2011) Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS ONE 6:e20471

    Article  PubMed  CAS  Google Scholar 

  17. Tian T, Xu Y, Dai J, Wu J, Shen H, Hu Z (2010) Functional polymorphisms in two pre-microRNAs and cancer risk: a meta-analysis. Int J Mol Epidemiol Genet 1:358–366

    PubMed  CAS  Google Scholar 

  18. Wang L, Qian S, Zhi H, Zhang Y, Wang B, Lu Z (2012) The association between hsa-miR-499T>C polymorphism and cancer risk: a meta-analysis. Gene 508:9–14

    Article  PubMed  CAS  Google Scholar 

  19. Akkiz H, Bayram S, Bekar A, Akgöllü E, Üsküdar O (2011) Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a Turkish population: lack of any association in a case–control study. Asian Pac J Cancer Prev 12:3107–3112

    PubMed  Google Scholar 

  20. Akkız H, Bayram S, Bekar A, Akgöllü E, Usküdar O, Sandıkçı M (2011) No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case–control study. Gene 486:104–109

    Article  PubMed  Google Scholar 

  21. Yue C, Wang M, Ding B, Wang W, Fu S, Zhou D, Zhang Z, Han S (2011) Polymorphism of the pre-miR-146a is associated with risk of cervical cancer in a Chinese population. Gynecol Oncol 122:33–37

    Article  PubMed  CAS  Google Scholar 

  22. Garcia AI, Cox DG, Barjhoux L, Verny-Pierre C, Barnes D, Gemo Study Collaborators, Antoniou AC, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S (2011) The rs2910164:G>C SNP in the MIR146A gene is not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum Mutat. doi:10.1002/humu.21539

  23. Zhou F, Zhu H, Luo D, Wang M, Dong X, Hong Y, Lu B, Zhou Y, Zhou J, Zhang Z, Gong W (2012) A functional polymorphism in Pre-miR-146a is associated with susceptibility to gastric cancer in a Chinese population. DNA Cell Biol 31:1290–1295

    Article  PubMed  CAS  Google Scholar 

  24. Lung RW, Wang X, Tong JH, Chau SL, Lau KM, Cheng SH, Woo JK, Woo J, Leung PC, Ng MH, Tang NL, To KF (2012) A single nucleotide polymorphism in microRNA-146a is associated with the risk for nasopharyngeal carcinoma. Mol Carcinog. doi: 10.1002/mc.21937

  25. Zhou J, Lv R, Song X, Li D, Hu X, Ying B, Wei Y, Wang L (2012) Association between two genetic variants in miRNA and primary liver cancer risk in the Chinese population. DNA Cell Biol 31:524–530

    Article  PubMed  CAS  Google Scholar 

  26. Xiang Y, Fan S, Cao J, Huang S, Zhang LP (2012) Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol Biol Rep 39:7019–7023

    Article  PubMed  CAS  Google Scholar 

  27. Kim WH, Min KT, Jeon YJ, Kwon CI, Ko KH, Park PW, Hong SP, Rim KS, Kwon SW, Hwang SG, Kim NK (2012) Association study of microRNA polymorphisms with hepatocellular carcinoma in Korean population. Gene 504:92–97

    Article  PubMed  CAS  Google Scholar 

  28. Liu Z, Li G, Wei S, Niu J, El-Naggar AK, Sturgis EM, Wei Q (2010) Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck. Cancer 116:4753–4760

    Article  PubMed  CAS  Google Scholar 

  29. Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D, Yonemura J, Ishizuka T, Arisawa T, Hirata I (2010) Association between common genetic variants in pre-microRNAs and gastric cancer risk in Japanese population. Helicobacter 15:524–531

    Article  PubMed  CAS  Google Scholar 

  30. George GP, Gangwar R, Mandal RK, Sankhwar SN, Mittal RD (2011) Genetic variation in microRNA genes and prostate cancer risk in North Indian population. Mol Biol Rep 38:1609–1615

    Article  PubMed  CAS  Google Scholar 

  31. Catucci I, Yang R, Verderio P, Pizzamiglio S, Heesen L, Hemminki K, Sutter C, Wappenschmidt B, Dick M, Arnold N, Bugert P, Niederacher D, Meindl A, Schmutzler RK, Bartram CC, Ficarazzi F, Tizzoni L, Zaffaroni D, Manoukian S, Barile M, Pierotti MA, Radice P, Burwinkel B, Peterlongo P (2010) Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance allelics in German and Italian familial breast cancer cases. Hum Mutat 31:E1052–E1057

    Article  PubMed  Google Scholar 

  32. Mittal RD, Gangwar R, George GP, Mittal T, Kapoor R (2011) Investigative role of pre-microRNAs in bladder cancer patients: a case–control study in North India. DNA Cell Biol 30:401–406

    Article  PubMed  CAS  Google Scholar 

  33. Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131

    Article  PubMed  CAS  Google Scholar 

  34. Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y (2009) microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 69:5970–5977

    Article  PubMed  CAS  Google Scholar 

  35. Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L, Wang B (2010) Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 16:3578–3583

    Article  PubMed  CAS  Google Scholar 

  36. Pastrello C, Polesel J, Della Puppa L, Viel A, Maestro R (2010) Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis 31:2124–2126

    Article  PubMed  CAS  Google Scholar 

  37. Guo H, Wang K, Xiong G, Hu H, Wang D, Xu X, Guan X, Yang K, Bai Y (2010) A functional varient in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Fam Cancer 9:599–603

    Article  PubMed  Google Scholar 

  38. Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD, Tong N, Wang JF, Song NH, Zhang W, Hua LX, Wu HF (2010) A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70:467–472

    Article  PubMed  CAS  Google Scholar 

  39. Permuth-Wey J, Thompson RC, Burton Nabors L, Olson JJ, Browning JE, Madden MH, Ann Chen Y, Egan KM (2011) A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma. J Neurooncol 105:639–646

    Article  PubMed  CAS  Google Scholar 

  40. Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K, Hamajima N (2011) Combined effect of miR-146a rs2910164 G/C polymorphism and Toll-like receptor 4 +3725 G/C polymorphism on the risk of severe gastric atrophy in Japanese. Dig Dis Sci 56:1131–1137

    Article  PubMed  CAS  Google Scholar 

  41. Wang Z, Cao Y, Jiang C, Yang G, Wu J, Ding Y (2012) Lack of association of two common polymorphisms rs2910164 and rs11614913 with susceptibility to hepatocellular carcinoma: a meta-analysis. PLoS One 7:e40039

    Google Scholar 

  42. Wang F, Sun G, Zou Y, Fan L, Song B (2012) Lack of association of miR-146a rs2910164 polymorphism with gastrointestinal cancers: evidence from 10206 subjects. PLoS One 7:e39623

    Google Scholar 

  43. Lian H, Wang L, Zhang J (2012) Increased risk of breast cancer associated with CC genotype of Has-miR-146a Rs2910164 polymorphism in Europeans. PLoS ONE 7:e31615

    Article  PubMed  CAS  Google Scholar 

  44. Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA 14:417–424

    Article  PubMed  CAS  Google Scholar 

  45. Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966

    Article  PubMed  CAS  Google Scholar 

  46. He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A (2005) The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075–19080

    Article  PubMed  CAS  Google Scholar 

  47. Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, Zheng ZM (2008) Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3:e2557

    Google Scholar 

  48. Hou Z, Xie L, Yu L, Qian X, Liu B (2012) MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis. Med Oncol 29:886–892

    Article  PubMed  CAS  Google Scholar 

  49. Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA, Sarkar FH (2010) miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res 70:1486–1495

    Article  PubMed  CAS  Google Scholar 

  50. Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaelian I, Mazoyer S (2011) Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med 3:279–290

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are most grateful to all the participants in the present study. This study was supported by grant no.81102194 from National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110001, People’s Republic of China

    Zhihua Yin, Xuelian Li, Yangwu Ren & Baosen Zhou

  2. Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, 110001, People’s Republic of China

    Zhihua Yin, Xuelian Li, Yangwu Ren & Baosen Zhou

  3. Department of Medical Informatics, China Medical University, Shenyang, 110001, People’s Republic of China

    Lei Yan

  4. China Medical University, Shenyang, 110001, People’s Republic of China

    Zhigang Cui

  5. Department of Epidemiology, Key Laboratory of Cancer Etiology and Intervention, China Medical University, University of Liaoning Province, No. 92, North Second Road, Heping District, Shenyang, 110001, People’s Republic of China

    Baosen Zhou

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  1. Zhihua Yin
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  2. Lei Yan
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  3. Zhigang Cui
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Correspondence to Baosen Zhou.

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Yin, Z., Yan, L., Cui, Z. et al. Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis. Mol Biol Rep 40, 3003–3013 (2013). https://doi.org/10.1007/s11033-012-2372-7

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  • DOI: https://doi.org/10.1007/s11033-012-2372-7

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