Methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms and bladder cancer susceptibility: A meta-analysis that includes race, smoking status and tumor stage

Abstract

Epidemiological studies have investigated that functional polymorphisms in methylene-tetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the several published studies have reported inconclusive results. The objective of the current study is to conduct an update analysis investigating the association between polymorphisms in MTHFR gene and the risk of bladder cancer. We searched the Pubmed database for all articles published up to March 31, 2011 that addressed the issue of bladder cancer and polymorphisms and variants or mutations of MTHFR. We perform a statistical analysis using STAT-A software. Two polymorphisms (C677T and A1298C) in 27 case-control studies from 15 articles that have been analyzed. The results indicated that individuals who carry the 677T allele (TC or TT+TC) have a 29% or 21% to develop bladder cancer compared to wild genotype (CC) in Mixed populations (OR: 0.71, 95%CI: 0.55-0.93; or OR: 0.79, 95%CI: 0.64-0.97, respectively). It is shown that there is significant positive associations between A1298C polymorphism and bladder cancer in Africans (OR: 1.24, 95%CI: 1.02-1.52 for C vs.A; OR: 1.35, 95%CI: 1.10-1.66 for CA vs. AA; OR: 1.29, 95%CI: 1.08-1.55 for CC+CA vs. AA). However, no significant relationship is found in two polymorphisms in the stratified analysis by smoking status. Interestingly, we indicate that individuals carrying 677T allele (TT+TC) have a higher percentage in invasive cases than superficial cases (OR: 1.38, 95%CI: 1.13-1.69). Results from the current new analysis suggest that C677T and A1298C polymorphisms in MTHFR gene are associated with bladder cancer risk and prognosis. Further evaluation based on more studies with larger groups of patients will be required in future research. Key words: Methylenetetrahydrofolate reductase, polymorphism, prognosis, susceptibility, meta-analysis.