Dataset Information

Genetic variants in microRNA target sites of 37 selected cancer-related genes and the risk of cervical cancer.

ABSTRACT:

Objectives

Single nucleotide polymorphisms (SNPs) in putative microRNA binding sites (miRSNPs) modulate cancer susceptibility via affecting miRNA binding. Here, we sought to investigate the association between miRSNPs and cervical cancer risk.

Methods

We first genotyped 41 miRSNPs of 37 cancer-related genes in 338 patients and 334 controls (Study 1), and replicated the significant associations in 502 patients and 600 controls (Study 2). We tested the effects of miRSNPs on microRNA-mRNA interaction by luciferase reporter assay.

Results

Five SNPs displayed notable association with cervical cancer risk in Study 1. Only IL-16 rs1131445 maintained a significant association with cervical cancer (CT/CC vs. TT, adjusted OR = 1.51, P = 0.001) in Study 2. This association was more evident in the combined data of two studies (adjusted OR = 1.49, P = 0.00007). We also found that miR-135b mimics interacted with IL-16 3'-UTR to reduce gene expression and that the rs1131445 T to C substitution within the putative binding site impaired the interaction of miR-135b with IL-16 3'-UTR. An ELISA indicated that the serum IL-16 of patients with cervical cancer was elevated (vs. controls, P = 0.001) and correlated with the rs1131445 genotype. Patients who carried the rs1131445 C allele had higher serum IL-16 than non-carriers (P<0.001).

Conclusions

These results support our hypothesis that miRSNPs constitute a susceptibility factor for cervical cancers. rs1131445 affects IL-16 expression by interfering with the suppressive function of miR135b and this variant is significantly associated with cervical cancer risk.

SUBMITTER: Mi Y

PROVIDER: S-EPMC3899132 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Genetic variants in microRNA target sites of 37 selected cancer-related genes and the risk of cervical cancer.

Mi Yang Y Wang Lijuan L Zong Lu L Pei Meili M Lu Qingyang Q Huang Pu P

PloS one 20140122 1

<h4>Objectives</h4>Single nucleotide polymorphisms (SNPs) in putative microRNA binding sites (miRSNPs) modulate cancer susceptibility via affecting miRNA binding. Here, we sought to investigate the association between miRSNPs and cervical cancer risk.<h4>Methods</h4>We first genotyped 41 miRSNPs of 37 cancer-related genes in 338 patients and 334 controls (Study 1), and replicated the significant associations in 502 patients and 600 controls (Study 2). We tested the effects of miRSNPs on microRNA ...[more]

PMID: 24465869

Similar Datasets

Project description:Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) may alter the processing, transcription, and expression of miRNAs and, thus, may contribute to cancer development. The authors hypothesized that common polymorphisms in pre-miRNAs are associated individually and (more likely) collectively with the risk of squamous cell carcinoma of the head and neck (SCCHN).The authors genotyped 4 common polymorphisms in pre-miRNAs: Homo sapiens miRNA 146a (hsa-mir-146a) (reference SNP 2910164 [rs2910164]; guanine to cytosine [G?C]), hsa-mir-149 (rs2292832; guanine to thymine [G?T]), hsa-mir-196a2 (rs11614913; C?T), and hsa-mir-499 (rs3746444; adenine to guanine [A?G]) in 1109 patients with SCCHN (cases) and in 1130 cancer-free patients (controls) in a non-Hispanic white population that was frequency-matched by age and sex. Univariate and multivariate logistic regression models were used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Of the 4 SNPs that were studied, the hsa-mir-499 AG and GG genotypes were associated with a reduced risk of SCCHN (OR, 0.83; 95% CI, 0.69-0.99). When the 4 SNPs were combined according to putative risk genotype, the number of observed risk genotypes was associated with an increased risk of SCCHN in a dose-response manner with ORs of 1.0, 1.20, and 1.40 for individuals who had 0 or 1 risk genotypes, 2 or 3 risk genotypes, and 4 risk genotypes, respectively (P(trend) = .037). Specifically, the risk was 1.23-fold (95% CI, 0.98-fold to 1.56-fold) for individuals with 2 to 4 risk genotypes and 1.40-fold (95% CI, 1.02-fold to 1.92-fold) for individuals who had 4 risk genotypes compared with individuals who had 0 or 1 risk genotypes. This risk was more pronounced in men and in patients with oropharyngeal cancer.The combined risk genotypes of 4 common SNPs in pre-miRNAs were associated significantly with a moderately increased risk of SCCHN. Larger studies are needed to validate the current findings.

Dataset Information

Genetic variants in microRNA target sites of 37 selected cancer-related genes and the risk of cervical cancer.

Objectives

Methods

Results

Conclusions

Publications

Genetic variants in microRNA target sites of 37 selected cancer-related genes and the risk of cervical cancer.

Similar Datasets

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