The MTHFR C677T Polymorphism and Prostate Cancer Risk: New Findings from a Meta-analysis of 7306 Cases and 8062 Controls

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a singlenucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases.We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statisticalrelationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094;CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343;Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observethe homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of thepolymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants’ residentialregion: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asianstudies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90],P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76],P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginalsignificance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphismagainst prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI =[0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI =[0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomenashould be viewed with the consideration of folate metabolism profile and different gene background as well asliving habits of different populations, and more relevant studies should be conducted to confirm our hypothesisand provide a comprehensive and clear picture concerning this topic.