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Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data

  • Research Article
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Tumor Biology

Abstract

The promoter region of the microRNA pri-miR-34b/c has a potentially functional polymorphism, rs4938723, located in a typical CpG island. Studies of the association between pri-miR-34b/c rs4938723 polymorphism and risks of various cancers have had inconsistent results. We therefore conducted a meta-analysis of nine studies that included 6,036 cancer patients and 7,490 controls to address this association. Overall, this meta-analysis showed the pri-miR-34b/c rs4938723 TC heterozygote to be significantly associated with increased risk of overall cancers compared with the wild-type TT genotype (P = 0.010, odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02–1.18). In stratified analysis, the TC heterozygote was significantly associated with increased cancers risks in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. The CC genotypes of rs4938723 were also associated with increased hepatocellular cancer risk but associated with decreased colorectal cancer risk in the stratification analysis by a single cancer type. Thus our meta-analysis suggests that the pri-miR-34b/c rs4938723 TC heterozygote contributes to increased overall cancer risks, as well as shown in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. This rs4938723 SNP showed an opposite tendency orientation between the hepatocellular cancer and colorectal cancer risks. Large-sample studies are needed to verify our findings.

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Abbreviations

SNP:

Single nucleotide polymorphism

OR:

Odds ratio

CI:

Confidence interval

HWE:

Hardy–Weinberg equilibrium

HB:

Hospital-based

PB:

Population-based

PCR-RFLP:

Restriction fragment length polymorphism-polymerase chain reaction

LDR:

Ligation detection reaction

References

  1. Mishra PJ, Humeniuk R, Mishra PJ, Longo-Sorbello GS, Banerjee D, Bertino JR. A mir-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci U S A. 2007;104:13513–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455:58–63.

    CAS  PubMed  Google Scholar 

  3. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455:64–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen CZ. MicroRNAs as oncogenes and tumor suppressors. N Engl J Med. 2005;353:1768–71.

    CAS  PubMed  Google Scholar 

  6. Duan R, Pak C, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet. 2007;16:1124–31.

    CAS  PubMed  Google Scholar 

  7. Xu L, Zhou X, Qiu MT, Yin R, Wu YQ, Xu L. Lack of association between hsa-miR-149 rs2292832 polymorphism and cancer risk: a meta-analysis of 12 studies. PLoS One. 2013;8:e73762.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Xu Q, He CY, Liu JW, Yuan Y. Pre-miR-27a rs895819A/G polymorphisms in cancer: a meta-analysis. PLoS One. 2013;8:e65208.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Hu M, Zhao L, Hu S, Yang J. The association between two common polymorphisms in microRNAs and hepatocellular carcinoma risk in Asian population. PLoS One. 2013;8:e57012.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Srivastava K, Srivastava A: Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. Plos One 2012;7.

  11. He B, Pan Y, Cho WC, Xu Y, Gu L, Nie Z, et al. The association between four genetic variants in microRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published studies. PLoS One. 2012;7:e49032.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, et al. Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS One. 2011;6:e20471.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bensen JT, Tse CK, Nyante SJ, Barnholtz-Sloan JS, Cole SR, Millikan RC. Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study. Cancer Causes Control. 2013;24:1099–109.

    PubMed  PubMed Central  Google Scholar 

  14. Xu Y, Liu L, Liu J, Zhang Y, Zhu J, Chen J, et al. A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma. Int J Cancer. 2011;128:412–7.

    PubMed  Google Scholar 

  15. Bossard P, Zaret KS. GATA transcription factors as potentiators of gut endoderm differentiation. Development. 1998;125:4909–17.

    CAS  PubMed  Google Scholar 

  16. Chou J, Provot S, Werb Z. GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol. 2010;222:42–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Han Y, Pu R, Han X, Zhao J, Zhang Y, Zhang Q, et al. Associations of pri-miR-34b/c and pre-miR-196a2 polymorphisms and their multiplicative interactions with hepatitis B virus mutations with hepatocellular carcinoma risk. PLoS One. 2013;8:e58564.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Li L, Wu J, Sima X, Bai P, Deng W, Deng X, et al. Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma. Tumour Biol. 2013;34:1919–23.

    CAS  PubMed  Google Scholar 

  19. Son MS, Jang MJ, Jeon YJ, Kim WH, Kwon CI, Ko KH, et al. Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma. Gene. 2013;524:156–60.

    CAS  PubMed  Google Scholar 

  20. Zhang S, Qian J, Cao Q, Li P, Wang M, Wang J, et al. A potentially functional polymorphism in the promoter region of miR-34b/c is associated with renal cell cancer risk in a Chinese population. Mutagenesis. 2014;29:149–54.

    CAS  PubMed  Google Scholar 

  21. Oh J, Kim JW, Lee BE, Jang MJ, Chong SY, Park PW, et al. Polymorphisms of the pri-miR-34b/c promoter and TP53 codon 72 are associated with risk of colorectal cancer. Oncol Rep. 2014;31:995–1002.

    CAS  PubMed  Google Scholar 

  22. Gao LB, Li LJ, Pan XM, Li ZH, Liang WB, Bai P, et al. A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer. Biol Chem. 2013;394:415–20.

    CAS  PubMed  Google Scholar 

  23. Yin J, Wang X, Zheng L, Shi Y, Wang L, Shao A, et al. Hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population. PLoS One. 2013;8:e80570.

    PubMed  PubMed Central  Google Scholar 

  24. Liang TJ, Liu HJ, Zhao XQ, Yu CH, Li CS. Lack of association of miR-34b/c polymorphism (rs4938723) with hepatocellular carcinoma: a meta-analysis. PLoS One. 2013;8:e68588.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, et al. Systematic review and meta-analysis of the association between {beta}2-adrenoceptor polymorphisms and asthma: a HuGe review. Am J Epidemiol. 2005;162:201–11.

    PubMed  Google Scholar 

  26. Gao LB, Pan XM, Li LJ, Liang WB, Zhu Y, Zhang LS, et al. RAD51 135 G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies. Breast Cancer Res Treat. 2011;125:827–35.

    CAS  PubMed  Google Scholar 

  27. Guo J, Jin M, Zhang M, Chen K. A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies. PLoS One. 2012;7:e30585.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    CAS  PubMed  Google Scholar 

  29. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    CAS  PubMed  Google Scholar 

  30. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    CAS  PubMed  Google Scholar 

  31. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Sevignani C, Calin GA, Nnadi SC, Shimizu M, Davuluri RV, Hyslop T, et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci U S A. 2007;104:8017–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Calin GA, Croce CM. Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest. 2007;117:2059–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, et al. P53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17:1298–307.

    CAS  PubMed  Google Scholar 

  36. He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26:731–43.

    CAS  PubMed  Google Scholar 

  39. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 2007;6:1586–93.

    CAS  PubMed  Google Scholar 

  40. Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67:8433–8.

    CAS  PubMed  Google Scholar 

  41. Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17:193–9.

    CAS  PubMed  Google Scholar 

  42. Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, et al. Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 2008;68:4123–32.

    CAS  PubMed  Google Scholar 

  43. Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 2008;68:2094–105.

    CAS  PubMed  Google Scholar 

  44. Ogawa R, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, et al. Expression profiling of micro-RNAs in human esophageal squamous cell carcinoma using RT-PCR. Med Mol Morphol. 2009;42:102–9.

    CAS  PubMed  Google Scholar 

  45. Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A. 2008;105:13556–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Chu H, Wang M, Shi D, Ma L, Zhang Z, Tong N, et al. Hsa-miR-196a2 rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies. PLoS One. 2011;6:e18108.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Wang Z, Wu J, Zhang G, Cao Y, Jiang C, Ding Y. Associations of miR-499 and miR-34b/c polymorphisms with susceptibility to hepatocellular carcinoma: an evidence-based evaluation. Gastroenterol Res Pract. 2013;2013:719202.

    PubMed  PubMed Central  Google Scholar 

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Conflicts of interest

None

Funding

This work is supported by Special Fund for Health Sector Scientific Research of the Ministry of Health (No. 201002004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Hepatobiliary Surgery and Department 1 of General Surgery, The First Affiliated Hospital of China Medical University, North Nanjing Street #155, Shenyang, 110001, Liaoning Province, China

    De-hui Yi, Ben-gang Wang, Xin-ping Zhong, Hao Liu & Yong-feng Liu

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  1. De-hui Yi
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  2. Ben-gang Wang
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  3. Xin-ping Zhong
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  4. Hao Liu
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  5. Yong-feng Liu
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Correspondence to Yong-feng Liu.

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Table S2

Scale for methodological quality assessment (DOC 39 kb)

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PRISMA 2009 Checklist (DOC 69 kb)

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Yi, Dh., Wang, Bg., Zhong, Xp. et al. Pri-miR-34b/c rs4938723 TC heterozygote is associated with increased cancer risks: evidence from published data. Tumor Biol. 35, 11967–11975 (2014). https://doi.org/10.1007/s13277-014-2493-9

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  • DOI: https://doi.org/10.1007/s13277-014-2493-9

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