Association of miR-126 and miR-143/145 Gene Polymorphisms with the Risk and Clinicopathological Features of Prostate Cancer

Document Type : Research Articles

Authors

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

2 Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

3 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Urology, Zahedan University of Medical Sciences, Zahedan, Iran.

Abstract

Background: Prostate cancer (PCa) represents a significant cause of morbidity and mortality among men. Recently, several biomarkers have been introduced to address the shortcomings in PCa management, including screening and diagnosis. MicroRNAs (miRNAs) are relatively novel biomarkers that may be dysregulated in PCa. However, the knowledge regarding the association between miRNA dysregulations and PCa remains limited in Iran. Methods: We performed a case-control analysis, comparing miR-126 rs4636297, miR-143/145 rs353292, miR-143/145 rs4705342, and miR-143/145 rs4705343 polymorphisms in 185 PCa patients and 220 cancer-free men based on DNA extracted from blood samples of Iranian subjects. Moreover, the correlation between clinicopathological features of PCa and these polymorphisms was  investigated. Results: miR-126 rs4636297 A>G, miR-143/145 rs353292 C>T, and miR-143/145 rs4705343 T>C variants were associated with a reduced risk of PCa in codominant, dominant, recessive, and allelic inheritance models. With the exception of the recessive inheritance pattern, the miR-143/145 rs4705342 T>C variant was also correlated with a reduced risk of PCa. Additionally, haplotype analysis of miR-143/145 (rs353292, rs4705342, and rs4705343, respectively) polymorphisms revealed that the CTT haplotype was the most frequent in cases and controls. Moreover, CTC, TTT, TCC, and TCT were associated with decreased risk of PCa. Finally, no relationship was identified between certain clinicopathological aspects of PCa and the mentioned polymorphisms. Conclusions: We identified several miR polymorphisms and distinct haplotypes associated with reduced PCa risk in a sample of the Iranian population. These findings pave the way for optimized PCa management and provide a better understanding of its pathophysiology. 

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