Association of Hsa-miR-23a rs3745453 variation with prostate cancer risk among Chinese Han population: A case-control study.

Minhao Zhang,Yali Wang,Chunhui Liu,Ming Chen,Zonghao You,Bin Xu,Can Wang,Shuqiu Chen,Qingfang Kong

doi:10.1097/md.0000000000018523

Minhao Zhang, Yali Wang + Show 7 more

Open Access

https://doi.org/10.1097/md.0000000000018523

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Abstract

Prostate cancer (PCa) is a frequently diagnosed malignant solid tumor in men. The etiology of PCa has been attributed to both environmental and genetic factors. In recent years, many studies have reported that miRNA gene single-nucleotide polymorphisms (SNPs) influence the susceptibility to several diseases such as cancer. To date, the mechanisms of PCa have remained unknown. The main aim of this study was to evaluate the association between PCa susceptibility and miRNA gene SNPs. A total of 156 PCa cases and 188 control subjects were included in this case-control study. The data were collected from hospitalized cases. We collected the demographic characteristic information, which included age, body mass index, tobacco smoking, alcohol consumption, and family history of cancer. Polymorphisms were analyzed by the ligase detection reaction. Unconditional logistic and stratified analyses were used to analyze the association between these SNPs and PCa susceptibility and to calculate the adjusted odds ratios (ORs) and the 95% confidence intervals (CIs). Cox regression model and the log-rank test were used to test the association between genetic variants and the overall survival. We found that miR-23a gene polymorphism rs3745453 carrying CC homozygotes had a 4.16-fold increased risk (95% CI = 1.30-13.25) than those carrying the TT/CT genotypes (P = .02), and the C allele displayed a higher prevalence of PCa than the T allele (OR = 1.68, 95% CI = 1.16-2.45, P = .01). Moreover, miR-23a showed that the homozygous carriers of the C-variant significantly increased the risk of survival rate as compared to the carriers of the TT/CT genotype (OR = 9.67, 95% CI = 2.83-33.09, P = .001). The rs3745453 polymorphism was potentially associated with PCa in the Chinese Han population and had an interactive relationship with the environmental factors.

Highlights

Prostate cancer (PCa) is the 2nd leading cause of cancer deaths in the United States
After stratification by cancer stage, pathologic classification (Gleason score: 7), peripheral blood prostate-specific antigen (PSA) level (20, >20), and PI-RADS score of magnetic resonance imaging (MRI) (
After the addition of potential covariates (CRPC occurrence time, survival time, outcome, cancer stage, age, body mass index (BMI), tobacco smoking, alcohol consumption, and a family history of cancer), we found that subjects carrying the CC homozygotes had a 9.67-fold increased risk as compared to those carrying the TT/CT genotypes (P = .001) in terms of the survival rate

Summary

Introduction

Prostate cancer (PCa) is the 2nd leading cause of cancer deaths in the United States. Previous studies have suggested that microRNAs (miRNAs) are involved in PCa carcinogenesis.[4,5] miRNAs are highly conserved, a class of naturally occurring, nonprotein-coding single-stranded RNAs with lengths of 21 to 24 nucleotides that can promote the degradation or inhibit the translation of target mRNAs at the posttranscription level.[6] miRNAs can regulate gene expression negatively and play a crucial role in gene regulation.[7] A previous study has reported that the proportion of coding protein genes regulated by the miRNAs in humans is 31%.[8] There is increasing evidence that miRNAs regulate bioprocesses such as progression, cell differentiation, proliferation, and apoptosis.[9]

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