Dataset Information

Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

ABSTRACT: Introduction:MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers. Aim:The present study investigated the genetic variants in pre-miRNAs (hsa-miRNA-196a2 rs11614913 C/T, hsa-miRNA-499 rs3746444 T/C and hsa-miRNA-146a rs2910164 G/C) for their role in cervical cancer susceptibility. Materials and Methods:The study comprised 164 controls and 184 patients of cervical cancer. The genotypic frequency of miRNA polymorphisms were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. Results:Hsa-miRNA-499 rs3746444 T/C polymorphism showed a statistically significant association with considerable risk for cervical cancer at genotypes (CC, p=0.001, OR=4.801) and variant allele (p<0.001, OR=2.307). MiRNA 146a and miRNA 196a2 polymorphisms showed no association with cervical cancer. However, interaction of miRNA polymorphisms with smoking habit showed higher risk of cervical cancer with miRNA 196a2 polymorphism in patients with smoking but no significant modification in the risk of cervical cancer was seen for other polymorphisms. Conclusion:The results of the present study demonstrate that, miRNA 499 T/C polymorphism is significantly associated with genetic susceptibility to cervical cancer and may have a role in its pathogenesis.

SUBMITTER: Srivastava S

PROVIDER: S-EPMC5713754 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

Srivastava Shruti S Singh Shalini S Fatima Naseem N Mittal Balraj B Srivastava Anand Narain AN

Journal of clinical and diagnostic research : JCDR 20170901 9

<h4>Introduction</h4>MicroRNAs (miRNAs) are short (~22 nucleotides) regulatory RNAs that can modulate gene expression and are aberrantly expressed in many diseases, including cancer. It has been suggested that, the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression and binding to target mRNA and represents another type of genetic variability, that can contribute to the susceptibility of human cancers.<h4>Aim</h4>The present study i ...[more]

PMID: 29207732

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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.

Project description:Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC.In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls.Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set.In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.

Dataset Information

Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

Publications

Pre-microRNA Gene Polymorphisms and Risk of Cervical Squamous Cell Carcinoma.

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