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Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer.

ABSTRACT: At present, inconsistent association between single nucleotide polymorphism (SNP) in pre-miRNAs (hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, and hsa-mir-146a rs2910164 C/G) and bladder cancer were obtained in limited studies. We performed a case-control study to test whether these three common polymorphisms are associated with bladder cancer. One hundred fifty-nine patients affected by bladder cancer and 298 unrelated healthy subjects were enrolled in the study.Using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP), genotypes of these three SNPs were determined, and their associations with bladder cancer, as well as with clinic pathological factors, and tumor progression were analyzed.No association between bladder cancer risk and variant allele of hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, or hsa-mir-146a rs2910164 C/G was observed. Heterozygous genotype (CT genotype) of rs11614913 was associated with a significantly decreased bladder cancer risk (P?=?0.004, OR?=?0.56, 95 % CI?=?0.38-0.83). Further stratified analyses showed that rs2910164 is associated with the tumor stage in a recessive model and with metastasis in a dominant model (P?=?0.012, OR?=?0.20, 95 % CI?=?0.05-0.72 and P?=?0.04, OR?=?2.63, 95 % CI?=?1.03-6.67, respectively). No association between hsa-mir-499 rs3746444 A/G and bladder cancer was observed.Our results suggested hsa-mir-196a2 rs11614913 C/T is associated with a significantly decreased risk of bladder cancer and hsa-mir-146a rs2910164 GG genotype is associated with clinical stage and metastasis in bladder cancer.

SUBMITTER: Deng S

PROVIDER: S-EPMC4603775 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer.

Deng Shi S Wang Wei W Li Xiang X Zhang Peng P

World journal of surgical oncology 20151013

<h4>Background</h4>At present, inconsistent association between single nucleotide polymorphism (SNP) in pre-miRNAs (hsa-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, and hsa-mir-146a rs2910164 C/G) and bladder cancer were obtained in limited studies. We performed a case-control study to test whether these three common polymorphisms are associated with bladder cancer. One hundred fifty-nine patients affected by bladder cancer and 298 unrelated healthy subjects were enrolled in the study.<h ...[more]

PMID: 26458899

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Project description:OBJECTIVE:MicroRNAs (miRNAs) are short regulatory RNAs that can modulate gene expression and function as negative regulators. Common genetic variants like single nucleotide polymorphisms (SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences in carcinogenesis. Therefore, we evaluated the genetic variants in pre-miRNAs: hsa-miR-146a G/C (rs2910164), hsa-miR-196a2 C/T (rs11614913), and hsa-miR-499 T>C (rs3746444) for their role in breast cancer susceptibility. STUDY DESIGN:The study comprised 121 breast cancer patients, 115 with benign breast disease, and 164 controls. The genotypic frequency of miRNA polymorphisms was determined by PCR-RFLP assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). RESULTS:The heterozygous variant of miR-146a G/C (rs2910164) is associated with the reduced risk of breast cancer at the genotype level as well as at the allele level (p < 0.05, OR = 0.5) as compared to controls. On the contrary, no significant difference was observed in the distribution of miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) polymorphisms in any groups both at genotype and allele levels. On the other hand, in multivariate analysis, we found that the miR-196a2 (rs11614913) C>T was associated with an increased risk of breast cancer risk in postmenopausal females (p = 0.02, OR = 3.2). We also attempted to find out the risk of malignant breast disease in relation to each of the above SNPs on dividing our data on the basis of benign and malignant status, but no significant difference was observed. In silico analysis using F-SNP showed change in transcriptional regulation by miR-146a G/C (rs2910164), miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) variations; the functional score was 0.100, 0.065 and 0.277, respectively. CONCLUSION:The results of the present study demonstrate that miR-146a G/C (rs2910164) polymorphism is associated with reduced genetic susceptibility to breast cancer. However, multivariate analysis showed as miR-196a2 (rs11614913) C>T to be associated with increased risk of breast cancer risk in postmenopausal females. Further multicentric studies involving a large number of cases need to be carried out to strengthen the present results.

Dataset Information

Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer.

Publications

Common genetic polymorphisms in pre-microRNAs and risk of bladder cancer.

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