Methionine Synthase Reductase-A66G and -C524T Single Nucleotide Polymorphisms and Prostate Cancer: A Case-Control Trial

Atefeh Basir

doi:10.31557/apjcp.2019.20.5.1445

Abstract

Purpose:Some variations in the sequence of methionine synthase reductase (MTRR) gene can increase the risk of various cancers such as prostate cancer. The aim of this study was to investigate the association between prostate cancer and the MTRR A66G and C524T gene single nucleotide polymorphisms (SNPs) using an in silico analysis.Methods:In this case-control study, 218 Iranian men, including 108 men with prostate cancer and 110 prostate cancer-free men, were enrolled. The MTRR A66G and C524T genotyping was performed by PCR-RFLP. Some of the bioinformatics tools were employed for the evaluation of polymorphism on the molecular aspects of the MTRR.Results:With regard to the MTRR A66G polymorphism, the genotype AG (OR: 0.85, 95% CI: 0.47-1.54, p= 0.6014), genotype GG (OR: 0.89, 95% CI: 0.42-1.87, p= 0.7512), and allele G (OR: 0.92, 95% CI: 0.63-1.35, p= 0.6686) were not associated with prostate cancer risk. However, the data for C524T SNP showed that the genotype CT was associated with prostate cancer risk (OR: 1.92, 95% CI: 1.06-3.47, p= 0.0308). Further, carriers of the allele T (OR: 1.80, 95% CI: 1.04-3.13, p= 0.0358) were associated with high risk of prostate cancer. In addition, bioinformatics analysis revealed that C524T SNP could affect some molecular aspects of the protein structure, while having no effect on the mRNA structure.Conclusion:The MTRR C524T is a genetic risk factor for prostate cancer; however, the MTRR A66G is not suggested as a suitable biomarker for prostate cancer. To obtain more reliable results, further studies are recommended to use larger sample sizes and investigate the effects of environmental factors.

Highlights

Prostate cancer is one of the leading causes of cancer death in men (Jemal et al, 2011; Karimian et al, 2018; Mazoochi et al, 2018)
The aim of the current study was to study the association between prostate cancer and A66G and C524T single nucleotide polymorphisms (SNPs) in the MTRR gene using an in silico approach
Our data showed that the genotype AG, genotype GG, and G allele were not associated with prostate cancer risk

Summary

Introduction

Prostate cancer is one of the leading causes of cancer death in men (Jemal et al, 2011; Karimian et al, 2018; Mazoochi et al, 2018). Folate pathway is essential for the maintenance of genome integrity (Donnelly, 2001; Fowler 2005; Karimian and Colagar, 2016), is involved in tumorigenicity, and plays an importance role in process of DNA repair and methylation (Kim et al, 2009). Studies suggest that folate deficiency is associated with increase of tumorigenesis risk in early stages, while excessive intake of folic acid might give rise to growth of malignant cells (Ulrich and Potter, 2007a). Folate intake before the presence of pre-neoplastic damage can inhibit tumor growth, while folate provision during establishment of primary damages seems to elevate tumor progression, suggesting the important role of folate function in synthesis of nucleotide. Proliferating tumor cells requires an elevated level of nucleotides; several malignancies up-regulate receptors of folate, and folate antagonists can be efficient in cancer therapy (Ulrich and Potter, 2007)

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