Association between MTHFR C677T Polymorphism and Risk of Prostate Cancer: Evidence from 22 Studies with 10,832 Cases and 11,993 Controls

Mehdi Abedinzadeh,Hormoz Karami,Masoud Zare-Shehneh,Maryam Abedinzadeh,Hossein Neamatzadeh

doi:10.7314/apjcp.2015.16.11.4525

Mehdi Abedinzadeh, Hormoz Karami + Show 3 more

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https://doi.org/10.7314/apjcp.2015.16.11.4525

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Abstract

The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved in folate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. A total of 22 independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. There was also no obvious association between MTHFR C677T polymorphism and risk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, Pheterogeneity =0.120, I2=45%), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, Pheterogeneity =0.587, I2=0.00%), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI= 1.233-2.367, P=0.001, Pheterogeneity =0.716, I2=0.00%), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, Pheterogeneity =0.462, I2=0.00%). These results suggest that the MTHFR C677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence in populations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostate cancer development in Asians.

Highlights

Prostate cancer is the most common malignancy and the second leading cause of cancer related death in men in indus¬trialized countries
The search strategy identified all possible studies using combinations of the following keywords: ‘‘methylenetetrahydrofolate reductase’’, ‘‘MTHFR’’, ‘‘MTHFR C677T’’, ‘‘folate’’, ‘‘one-carbon metabolism’’, ‘‘rs1801133’’, ‘‘polymorphism’’, ‘‘genotype’’, and ‘’prostate cancer’’ All references cited in the included studies were hand-searched and reviewed to identify additional published articles not indexed in common databases
Inclusion and exclusion criteria Studies included in this meta-analysis had to meet the following criteria: (1) evaluate the MTHFR C677T polymorphism and prostate cancer risk, (2) only cohort studies and case control studies were included in this meta-analysis; (3) Provision of information on genotype frequencies of the MTHFR C677T polymorphism and sufficient data for the calculation

Summary

Introduction

Prostate cancer is the most common malignancy and the second leading cause of cancer related death in men in indus¬trialized countries. Genome-wide association studies have identified several genetic variants that each slightly increases prostate cancer risk (Eeles 2t al, 2008). The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, Pheterogeneity =0.120, I2=45%), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, Pheterogeneity =0.587, I2=0.00%), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI= 1.233-2.367, P=0.001, Pheterogeneity =0.716, I2=0.00%), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, Pheterogeneity =0.462, I2=0.00%). The meta analysis indicates that it may play a role in prostate cancer development in Asians

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