Lack of association between MTHFR Ala222Val and Glu429Ala polymorphisms and bladder cancer risk: A meta-analysis of case-control studies

Abstract

Bladder cancer is a commom malignancy in the urinary tract that is influenced by genetic and environmental factors. The role of functional polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene with bladder cancer risk remains to be determined. This meta-analysis was performed to derive a more precise estimation of MTHFR Ala222Val and Glu429Ala polymorphisms and bladder cancer risk. Data were collected with the last report up to September 2013. A total of 3,463 cases and 3,927 controls for Ala222Val, and 3,177 cases and 3,502 controls for Glu429Ala were analyzed. The pooled odds ratios (ORs) and 95% confidence interval (CI) were estimated for the association with bladder cancer risk. Overall, no significant associations of Ala222Val and Glu429Ala polymorphisms with bladder cancer risk were found (for Ala222Val: Val/Val vs. Ala/Ala: OR, 1.02; 95% CI: 0.80-1.29; Val/Ala vs. Ala/Ala: OR, 1.02; 95% CI: 0.92-1.12; dominant model: OR, 1.01; 95% CI: 0.87-1.17; recessive model: OR, 1.00; 95% CI: 0.87-1.15; and for Glu429Ala: Ala/Ala vs. Glu/Glu: OR, 1.11; 95% CI: 0.78-1.58; Ala/Glu vs. Glu/Glu: OR, 1.16; 95% CI: 0.95-1.40; dominant model: OR, 1.15; 95% CI: 0.94-1.41; recessive model: OR, 0.96; 95% CI: 0.79-1.15). In stratified analyses by ethnicity, significant associations were observed for Glu429Ala polymorphism in individuals of Middle Eastern descent (Ala/Glu vs. Glu/Glu: OR, 2.11; 95% CI: 1.26-3.53; dominant model: OR, 2.16; 95% CI: 1.16-4.01; recessive model: OR, 1.82; 95% CI: 1.11-3.01). This meta-analysis demonstrated that overall there was no association of MTHFR Ala222Val and Glu429Ala polymorphisms with bladder cancer risk. However, in the stratified analysis by ethnicity the MTHFR Glu429Ala polymorphism was significantly associated with increased bladder cancer risk in individuals of Middle Eastern descent.

Keywords: bladder cancer; meta-analysis; methylenetetrahydrofolate reductase; polymorphism.

Figure 1

Forest plots of methylenetetrahydrofolate reductase (MTHFR) Glu429Ala polymorphism and bladder cancer risk when stratified by ethnicity. (A) Ala/Glu vs. Glu/Glu, (B) dominant model and (C) recessive model, respectively.

Figure 1

Forest plots of methylenetetrahydrofolate reductase (MTHFR) Glu429Ala polymorphism and bladder cancer risk when stratified by ethnicity. (A) Ala/Glu vs. Glu/Glu, (B) dominant model and (C) recessive model, respectively.

Figure 1

Forest plots of methylenetetrahydrofolate reductase (MTHFR) Glu429Ala polymorphism and bladder cancer risk when stratified by ethnicity. (A) Ala/Glu vs. Glu/Glu, (B) dominant model and (C) recessive model, respectively.

Figure 2

Funnel plot analysis for odds ratios (ORs). Recessive genetic model of methylenetetrahydrofolate reductase (MTHFR) Glu429Ala polymorphism in overall studies is shown as an example.