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hsa-mir-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population

    Mohsen Omrani

    Cellular & Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

    Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    ,
    Mohammad Hashemi

    * Author for correspondence

    Cellular & Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

    ,
    Ebrahim Eskandari-Nasab

    Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    ,
    Seyed-Shahaboddin Hasani

    Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    ,
    Mohammad Ali Mashhadi

    Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    ,
    Farshid Arbabi

    Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    &
    Mohsen Taheri

    Genetics of Non Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

    Published Online:https://doi.org/10.2217/bmm.13.118

    Aim: Our study aimed to evaluate the possible association between four miRNA polymorphisms, hsa-miR-146a (rs2910164 G>C), hsa-miR-499 (rs3746444 T>C) and hsa-miRNA-196a2 (rs11614913 C>T and rs185070757 T>G), and susceptibility to breast cancer in an Iranian population. Materials & methods: In this case–control study we enrolled 236 patients with breast cancer and 203 healthy individuals. Tetra primer amplification refractory mutation system PCR was applied for genotyping the four miRNA SNPs. Results: Our study indicated that the hsa-mir-499 rs3746444 CC homozygote increased the risk of breast cancer in the dominant (odds ratio [OR]: 2.42; 95% CI: 1.43–4.09; p = 0.001; CC vs TT) and recessive (OR: 2.48; 95% CI: 1.49–4.13; p = 0.004; CC vs TT+TC) inheritance models tested. In addition, the rs3746444 C allele increased the risk of breast cancer (OR: 1.71; 95% CI: 1.27–2.29; p = 0.0004) in comparison with the T allele. However, distribution of the rs2910164 G>C, rs11614913 C>T and rs185070757 T>G genotypes was not statistically different between cases and controls (p > 0.05). Conclusion: Our findings demonstrated that the hsa-mir-499 rs3746444 polymorphism is associated with higher risk of developing breast cancer in our population.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

    References

    • Hashemi M, Eskandari-Nasab E, Fazaeli A et al. Association between polymorphisms of glutathione S-transferase genes (GSTM1, GSTP1 and GSTT1) and breast cancer risk in a sample Iranian population. Biomarkers Med.6(6),797–803 (2012).Link, CASGoogle Scholar
    • Eskandari-Nasab E, Hashemi M, Rezaei H et al. Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer. Mol. Biol. Rep.39(12),10531–10539 (2012).Crossref, Medline, CASGoogle Scholar
    • Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. miRNAs and related polymorphisms in rheumatoid arthritis susceptibility. Autoimmun. Rev.11,639–641 (2012).▪ Discusses the importance of various miRNAs and related polymorphisms in rheumatoid arthritis susceptibility.CrossrefGoogle Scholar
    • Hashemi M, Eskandari-Nasab E, Zakeri Z et al. Association of pre-miRNA-146a rs2910164 and premiRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis. Mol. Med. Rep.7(1),287–291 (2012).Crossref, MedlineGoogle Scholar
    • Hua Z, Chun W, Fang-Yuan C. MicroRNA-146a and hemopoietic disorders. Int. J. Hematol.94(3),224–229 (2011).▪▪ Focuses on recent progress in analyzing the functional roles of miR-146a in normal hematopoiesis and hematopoietic disease.Crossref, MedlineGoogle Scholar
    • Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin. Cancer Res.18(4),981–992 (2012).Crossref, Medline, CASGoogle Scholar
    • Wang Y, Li Z, He C et al. MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cells Mol. Dis.44(3),191–197 (2010).Crossref, Medline, CASGoogle Scholar
    • Shin KC, Choi EY, Chung JH, Jeon C, Lee KH. Clinical application of MAGE A1-6 RT-nested PCR for diagnosis of lung cancer invisible by bronchoscopy. Anticancer Res.32(1),163–167 (2012).MedlineGoogle Scholar
    • Hu Z, Liang J, Wang Z et al. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum. Mutat.30(1),79–84 (2009).Crossref, Medline, CASGoogle Scholar
    • 10  Wang Y, Yang B, Ren X. Hsa-miR-499 polymorphism (rs3746444) and cancer risk: a meta-analysis of 17 case–control studies. Gene509(2),267–272 (2012).▪ Meta-analysis demonstrating that the hsa-miR-499 rs3746444 polymorphism contributes to the susceptibility of cancers.Crossref, Medline, CASGoogle Scholar
    • 11  Wang L, Qian S, Zhi H, Zhang Y, Wang B, Lu Z. The association between hsa-miR-499 T>C polymorphism and cancer risk: a meta-analysis. Gene508(1),9–14 (2012).Crossref, Medline, CASGoogle Scholar
    • 12  Zhao S, Liu Y, Zhang Q et al. The prognostic role of circulating tumor cells (CTCs) detected by RT-PCR in breast cancer: a meta-analysis of published literature. Breast Cancer Res. Treat.130(3),809–816 (2011).Crossref, MedlineGoogle Scholar
    • 13  Williams AE, Perry MM, Moschos SA, Larner-Svensson HM, Lindsay MA. Role of miRNA-146a in the regulation of the innate immune response and cancer. Biochem. Soc. Trans.36(Pt 6),1211–1215 (2008).▪ Reviewed the evidence for a role of miR-146a in innate immunity and cancer, and assessed whether changes in miR-146a might link these two biological responses.Crossref, Medline, CASGoogle Scholar
    • 14  Garcia AI, Cox DG, Barjhoux L et al. The rs2910164:G>C SNP in the MIR146A gene is not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Hum. Mutat.32(9),1004–1007 (2011).Crossref, Medline, CASGoogle Scholar
    • 15  Tanic M, Zajac M, Gomez-Lopez G, Benitez J, Martinez-Delgado B. Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFkappaB pathway. Breast Cancer Res. Treat.134(1),41–51 (2011).Crossref, MedlineGoogle Scholar
    • 16  Matei MC, Negura L, Liliac L, Negura A, Azoicai D. Validation of PCR-RFLP techniques for the evaluation of codon 72 of p53 and CYP1A1 gene’s polymorphisms in relation with ovarian cancer in a Romanian population. Rom. J. Morphol. Embryol.53(1),47–54 (2012).MedlineGoogle Scholar
    • 17  Christoffersen NR, Shalgi R, Frankel LB et al. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ.17(2),236–245 (2010).Crossref, Medline, CASGoogle Scholar
    • 18  Jegg AM, Ward TM, Iorns E et al. PI3K independent activation of mTORC1 as a target in lapatinib-resistant ERBB2+ breast cancer cells. Breast Cancer Res. Treat.136(3),683–692 (2012).Crossref, Medline, CASGoogle Scholar
    • 19  De La Chapelle A, Jazdzewski K. MicroRNAs in thyroid cancer. J. Clin. Endocrinol. Metab.96(11),3326–3336 (2011).Crossref, Medline, CASGoogle Scholar
    • 20  Liu Z, Li G, Wei S et al. Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck. Cancer116(20),4753–4760 (2010).Crossref, Medline, CASGoogle Scholar
    • 21  Catucci I, Yang R, Verderio P et al. Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases. Hum. Mutat.31(1),e1052–e1057 (2010).▪ Suggested a lack of association between the SNPs rs2910164, rs11614913 and rs3746444 and breast cancer risk, or age at breast cancer onset.Crossref, MedlineGoogle Scholar
    • 22  Xiang Y, Fan S, Cao J, Huang S, Zhang LP. Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol. Biol. Rep.39(6),7019–7023 (2012).Crossref, Medline, CASGoogle Scholar
    • 23  Yang L, Li Y, Cheng M et al. A functional polymorphism at microRNA-629-binding site in the 3´-untranslated region of NBS1 gene confers an increased risk of lung cancer in southern and eastern Chinese population. Carcinogenesis33(2),338–347 (2012).Crossref, Medline, CASGoogle Scholar
    • 24  Mittal RD, Gangwar R, George GP, Mittal T, Kapoor R. Investigative role of pre-microRNAs in bladder cancer patients: a case–control study in north India. DNA Cell Biol.30(6),401–406 (2011).Crossref, Medline, CASGoogle Scholar
    • 25  Lian H, Wang L, Zhang J. Increased risk of breast cancer associated with CC genotype of Has-miR-146a rs2910164 polymorphism in Europeans. PLoS ONE7(2),e31615 (2012).Crossref, Medline, CASGoogle Scholar
    • 26  Pastrello C, Polesel J, Della Puppa L, Viel A, Maestro R. Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis31(12),2124–2126 (2010).Crossref, Medline, CASGoogle Scholar
    • 27  Zhi H, Wang L, Ma G et al. Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease. Clin. Res. Cardiol.101(4),289–296 (2011).Crossref, MedlineGoogle Scholar
    • 28  Xiang Y, Fan S, Cao J, Huang S, Zhang LP. Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol. Biol. Rep.39(6),7019–7023 (2012).Crossref, Medline, CASGoogle Scholar
    • 29  Gao LB, Bai P, Pan XM et al. The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis. Breast Cancer Res. Treat.125(2),571–574 (2011).Crossref, MedlineGoogle Scholar
    • 30  Hashemi M, Moazeni-Roodi AK, Fazaeli A et al. Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran. Genet. Mol. Res.9(1),333–339 (2010).Crossref, Medline, CASGoogle Scholar
    • 31  Hashemi M, Moazeni-Roodi A, Bahari A, Taheri M. A tetra-primer amplification refractory mutation system-polymerase chain reaction for the detection of rs8099917 IL28B genotype. Nucleosides Nucleotides Nucleic Acids31(1),55–60 (2012).Crossref, Medline, CASGoogle Scholar
    • 32  Hashemi M, Hoseini H, Yaghmaei P et al. Association of polymorphisms in glutamate–cysteine ligase catalytic subunit and microsomal triglyceride transfer protein genes with nonalcoholic fatty liver disease. DNA Cell Biol.30(8),569–575 (2011).Crossref, Medline, CASGoogle Scholar
    • 33  Li L, Chen XP, Li YJ. MicroRNA-146a and human disease. Scand. J. Immunol.71(4),227–231 (2010).Crossref, Medline, CASGoogle Scholar
    • 34  Li J, Wan Y, Guo Q et al. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res. Ther.12(3),R81 (2010).▪ Indicates a role for miR-146a in rheumatoid arthritis pathogenesis and provides potential novel therapeutic targets.Crossref, Medline, CASGoogle Scholar
    • 35  Wang F, Sun G, Zou Y, Li Y, Hao L, Pan F. Association of microRNA-499 rs3746444 polymorphism with cancer risk: evidence from 7188 cases and 8548 controls. PLoS ONE7(9),e45042 (2012).Crossref, Medline, CASGoogle Scholar
    • 36  Wang J, Wang Q, Liu H et al. The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms with cancer risk: a meta-analysis of 32 studies. Mutagenesis27(6),779–788 (2012).Crossref, Medline, CASGoogle Scholar
    • 37  Xu W, Xu J, Liu S et al. Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: a meta-analysis. PLoS ONE6(5),e20471 (2011).Crossref, Medline, CASGoogle Scholar
    • 38  Wang J, Bi J, Liu X, Li K, Di J, Wang B. Has-miR-146a polymorphism (rs2910164) and cancer risk: a meta-analysis of 19 case–control studies. Mol. Biol. Rep.39(4),4571–4579 (2012).Crossref, Medline, CASGoogle Scholar
    • 39  Qiu LX, He J, Wang MY et al. The association between common genetic variant of microRNA-146a and cancer susceptibility. Cytokine56(3),695–698 (2011).Crossref, Medline, CASGoogle Scholar
    • 40  Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis29(10),1963–1966 (2008).Crossref, Medline, CASGoogle Scholar
    • 41  Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. miRNAs and related polymorphisms in rheumatoid arthritis susceptibility. Autoimmun. Rev.11(9),636–641 (2012).Crossref, Medline, CASGoogle Scholar
    • 42  Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res. Ther.10(4),R101 (2008).▪ Suggests a possible mechanism contributing to rheumatoid arthritis pathogenesis, which leads to prolonged TNF-α production in patients with rheumatoid arthritis.Crossref, MedlineGoogle Scholar
    • 43  Nahid MA, Satoh M, Chan EK. MicroRNA in TLR signaling and endotoxin tolerance. Cell. Mol. Immunol.8(5),388–403 (2011).Crossref, Medline, CASGoogle Scholar
    • 44  Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. The role of microRNA-146a (miR-146a) and its target IL-1R-associated kinase (IRAK1) in psoriatic arthritis susceptibility. Scand. J. Immunol.71(5),382–385 (2010).Crossref, Medline, CASGoogle Scholar
    • 45  Boldin MP, Taganov KD, Rao DS et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J. Exp. Med.208(6),1189–1201 (2011).▪ Suggests that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation and oncogenic transformation.Crossref, Medline, CASGoogle Scholar
    • 46  Wang AX, Xu B, Tong N et al. Meta-analysis confirms that a common G/C variant in the pre-miR-146a gene contributes to cancer susceptibility and that ethnicity, gender and smoking status are risk factors. Genet. Mol. Res.11(3),3051–3062 (2012).Crossref, Medline, CASGoogle Scholar
    • 47  Landgraf P, Rusu M, Sheridan R et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell129(7),1401–1414 (2007).Crossref, Medline, CASGoogle Scholar
    • 48  Desjardins S, Beauparlant JC, Labrie Y, Ouellette G, Durocher F. Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer. BMC Cancer9,181 (2009).Crossref, MedlineGoogle Scholar
    • 49  Pickard MR, Green AR, Ellis IO et al. Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer. Breast Cancer Res.11(4),R60 (2009).Crossref, MedlineGoogle Scholar
    • 50  Alshatwi AA, Shafi G, Hasan TN et al. Differential expression profile and genetic variants of microRNAs sequences in breast cancer patients. PLoS ONE7(2),e30049 (2012).Crossref, Medline, CASGoogle Scholar