Association between the DICER rs1057035 Polymorphism and Cancer Risk: Evidence from a Meta-analysis of 1,2675 Individuals

  • Yu, Yan-Yan (Chengdu Municipal Center for Disease Control and Prevention) ;
  • Kuang, Dan (Chengdu Municipal Center for Disease Control and Prevention) ;
  • Yin, Xiao-Xv (School of Public Health, Tongji Medical College, Huazhong University of Science and Technology)
  • Published : 2015.02.04


Background: DICER, one of the microRNA (miRNA) biogenesis proteins, is involved in the maturation of miRNAs and is implicated in cancer development and progression. The results from previous epidemiological studies on associations between DICER rs1057035 polymorphism and cancer risk were inconsistent. Thereforewe performed this meta-analysis to summarize possible associations. Materials and Methods: We searched all relevant articles on associations between DICER rs1057035 polymorphism and cancer risk from PubMed, EMBASE, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure until August 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess any associations. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in this meta-analysis. All analyses were conducted using STATA software. Results: Seven case-control studies, including 4,875 cancer cases and 7,800 controls were included in the meta-analysis. Overall, the results indicated that the C allele of DICER rs1057035 polymorphism was significantly associated with decreased cancer risk in allelic comparison, heterozygote and dominant genetic models (C vs T: OR=0.88, 95%CI 0.81-0.95, p=0.002; TC vs TT: OR=0.85, 95%CI 0.77-0.93, p=0.001; CC/TC vs TT: OR=0.86, 95%CI 0.78-0.94, p=0.001). In the subgroup analysis by ethnicity, a significantly decreased cancer risk was found in Asian but not Caucasian populations. Conclusions: The present meta-analysis suggests that the C allele of the DICER rs1057035 polymorphism probably decreases cancer risk. However, this association may be Asian-specific and the results should be treated with caution. Further well-designed studies based on larger sample sizes and group of populations are needed to validate these findings.


  1. Ambros V (2004). The functions of animal microRNAs. Nature, 431, 350-5.
  2. Avery-Kiejda KA, Braye SG, Forbes JF, et al (2014). The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer. BMC Cancer, 14, 253.
  3. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  4. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.
  5. Bian XJ, Zhang GM, Gu CY, et al (2014). Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer. Tumour Biol.
  6. Blaszczyk J, Tropea JE, Bubunenko M, et al (2001). Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage. Structure, 9, 1225-36.
  7. Caffrey E, Ingoldsby H, Wall D, et al (2013). Prognostic significance of deregulated dicer expression in breast cancer. PLoS One, 8, 83724.
  8. Carthew RW (2006). Gene regulation by microRNAs. Curr Opin Genet Dev, 16, 203-8.
  9. Chen J, Qin Z, Pan S, et al (2013). Genetic variants in RAN, DICER and HIWI of microRNA biogenesis genes and risk of cervical carcinoma in a Chinese population. Chin J Cancer Res, 25, 565-71.
  10. Cui SY, Wang R, Chen LB (2014). MicroRNA-145: a potent tumour suppressor that regulates multiple cellular pathways. J Cell Mol Med, 18, 1913-26.
  11. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  12. Donadelli M, Dando I, Fiorini C, et al (2014). Regulation of miR-23b expression and its dual role on ROS production and tumour development. Cancer Lett, 349, 107-13.
  13. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  14. Gao C, Li X, Tong B, et al (2014). Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous cell carcinoma. Acta Otolaryngol, 134, 959-63.
  15. Gu J, Chen Y, Huang H, et al (2014). Gene module based regulator inference identifying miR-139 as a tumor suppressor in colorectal cancer. Mol Biosyst, 10, 3249-54.
  16. Guo B, Li J, Liu L, et al (2013). Dysregulation of miRNAs and their potential as biomarkers for the diagnosis of gastric cancer. Biomed Rep, 1, 907-12.
  17. He L, Wang HY, Zhang L, et al (2014). Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer. Cell Death Dis, 5, 1205.
  18. Higgins J, Thompson S, Deeks J, et al (2002). Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy, 7, 51-61.
  19. Hu CB, Li QL, Hu JF, et al (2014). miR-124 inhibits growth and invasion of gastric cancer by targeting ROCK1. Asian Pac J Cancer Prev, 15, 6543-6.
  20. Jiang Y, Chen J, Wu J, et al (2013). Evaluation of genetic variants in microRNA biosynthesis genes and risk of breast cancer in Chinese women. Int J Cancer, 133, 2216-24.
  21. Kavitha N, Vijayarathna S, Jothy SL, et al (2014). MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis. Asian Pac J Cancer Prev, 15, 7489-97.
  22. Lee Y, Kim M, Han J, et al (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23, 4051-60.
  23. Li M, Guan X, Sun Y, et al (2014). miR-92a family and their target genes in tumorigenesis and metastasis. Exp Cell Res, 323, 1-6.
  24. Li Y, Xu Z, Wang K, et al (2013). Network analysis of microRNAs, genes and their regulation in human bladder cancer. Biomed Rep, 1, 918-24.
  25. Liu L, An J, Liu J, et al (2013). Potentially functional genetic variants in microRNA processing genes and risk of HBVrelated hepatocellular carcinoma. Mol Carcinog, 52, 148-54.
  26. Liu X, Fortin K, Mourelatos Z (2008). MicroRNAs: biogenesis and molecular functions. Brain Pathol, 18, 113-21.
  27. Lyle S, Hoover K, Colpan C, et al (2014). Dicer cooperates with p53 to suppress DNA damage and skin carcinogenesis in mice. PLoS One, 9, 100920.
  28. Ma H, Yuan H, Yuan Z, et al (2012). Genetic variations in key microRNA processing genes and risk of head and neck cancer: a case-control study in Chinese population. PLoS One, 7, 47544.
  29. Orang AV, Barzegari A (2014). MicroRNAs in colorectal cancer: from diagnosis to targeted therapy. Asian Pac J Cancer Prev, 15, 6989-99.
  30. Schaid DJ, Jacobsen SJ (1999). Biased tests of association: comparisons of allele frequencies when departing from Hardy-Weinberg proportions. Am J Epidemiol, 149, 706-11.
  31. Slaby O, Sachlova M, Brezkova V, et al (2013). Identification of microRNAs regulated by isothiocyanates and association of polymorphisms inside their target sites with risk of sporadic colorectal cancer. Nutr Cancer, 65, 247-54.
  32. Tufekci KU, Meuwissen RL, Genc S (2014). The role of microRNAs in biological processes. Methods Mol Biol, 1107, 15-31.
  33. Xiu Y, Liu Z, Xia S, et al (2014). MicroRNA-137 Upregulation Increases Bladder Cancer Cell Proliferation and Invasion by Targeting PAQR3. PLoS One, 9, 109734.
  34. Yuan L, Chu H, Wang M, et al (2013). Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk. PLoS One, 8, 81524.
  35. Zamore PD, Haley B (2005). Ribo-gnome: the big world of small RNAs. Science, 309, 1519-24.
  36. Zintzaras E, Ioannidis JP (2005). HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics, 21, 3672-3.

Cited by

  1. Association of rs1057035polymorphism in microRNA biogenesis pathway gene (DICER1) with azoospermia among Iranian population pp.2092-9293, 2017,