Systematic evaluation of cancer risk associated with DNMT3B polymorphisms.

Abstract

The aim of our study is to provide a precise quantification for the association between DNA methyltransferase 3B (DNMT3B) variations (rs2424913 C/T, rs1569686 G/T, rs6087990 T/C and rs2424908 T/C) and the risk of cancer. We performed a systematic literature review and assessed the methodological quality of included case-control designed studies based on Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 34 studies for pooled analyses. Overall, the results demonstrated that rs2424913 polymorphism was significantly associated with negative cancer risk in the African population (CT vs TT: OR 0.10, 95% CI 0.02-0.63, P = 0.01; CT+CC vs TT: OR 0.14, 95% CI 0.03-0.76, P = 0.02), and the rs1569686 polymorphism was significantly associated with a subtly decreased cancer risk (GT vs TT: OR 0.80, 95% CI 0.72-0.90, P < 0.01; GT+GG vs TT: OR 0.84, 95% CI 0.76-0.94, P < 0.01), particularly in the Asian population (GT vs TT: OR 0.79, 95% CI 0.66-0.96, P < 0.01) and in colorectal cancer subgroup (G vs T: OR 0.69, 95% CI 0.54-0.88, P < 0.01). In addition, the rs6087990 polymorphism was associated with decreased risk in Asian population (T vs C: OR 0.77, 95% CI 0.62-0.96, P = 0.02). Similarly, the rs2424908 polymorphism was observed as a protective factor for cancer in the Asian population (CT+CC vs TT: OR 0.79, 95% CI 0.66-0.95, P = 0.01). DNMT3B polymorphisms might be associated with decreased cancer risk especially in the Asian population and for colorectal cancer. Further multicentric studies are still needed to confirm the results.