MTHFR functional polymorphisms and haplotypes are a risk factor for urinary bladder cancer: a case-control study and meta-analysis

MTHFR polymorphisms and urinary bladder cancer

Abstract

Background: A subtle modification in the genes coding for enzymes responsible for DNA synthesis, DNA repair and methylation can modify their activity, which eventually affects the susceptibility and sensitivity of an individual towards cancer. Methylene-tetrahydrofolate reductase (MTHFR) plays a crucial role in DNA synthesis and methylation reactions and genetic variations in this gene may associate with the cancer susceptibility. The present study analyzed three polymorphisms (c.677C>T, c.1298A>C and c.203G>A) in the MTHFR gene for correlation with the risk of urinary bladder cancer (UBC).

Methods: Genotyping of the three polymorphisms was performed in 232 cases and 250 controls by direct DNA sequencing method. For meta-analysis, the relevant data were collected through literature search in Pubmed, ScienceDirect and Google Scholar databases using the keywords, methylene-tetrahydrofolatereductase, MTHFR, c.677C>T polymorphism, c.1298A>C polymorphism and urinary bladder cancer in various combinations.

Results: We observed a significant protective association of c.1298A>C with bladder cancer risk, but c.677C>T and c.203G>A were unrelated to the UBC risk. We also undertook a meta-analysis on 4171 cases and 4749 controls for c.677C>T polymorphism and on 3785 cases and 4205 controls for c.1298A>C polymorphism. The meta-analysis revealed a lack of association of these polymorphisms with the UBC risk.

Conclusion: MTHFR c.1298A>C substitution is protective against urinary bladder cancer in the study population; however, meta-analysis denied an association at the global level.