Association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma susceptibility: evidence from a meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. A number of studies have examined the association of MTHFR C677T and A1298C polymorphisms with non-Hodgkin lymphoma (NHL) susceptibility; however, the conclusions were contradictory. We searched available publications assessing the polymorphisms of MTHFR and NHL susceptibility from MEDLINE, EMBASE and CBM. Genotype-based mRNA expression analysis was performed using data from 270 individuals with three different ethnicities. Ultimately, a total of 7448 cases and 11146 controls from 25 studies were included for the C677T polymorphism, 6173 cases and 9725 controls from 19 studies for the A1298C polymorphism. Pooled results indicated that neither C677T nor A1298C polymorphism was associated with NHL susceptibility. However, C677T polymorphism showed a statistically significantly increased risk for Caucasians, but a decreased risk for Asians in the subgroup analysis by ethnicity. The same variants may confer increased susceptibility to develop follicular lymphoma (FL). Moreover, A1298C polymorphism was associated with increased NHL risk for Asians. This meta-analysis indicated that C677T polymorphism was associated with altered NHL susceptibility for Caucasians, Asians and FL. Increased NHL risk was also shown for A1298C among Asians. These findings warrant validation in large and well-designed prospective studies.