Folate (MTHFR C677T and MTRR A66G) gene polymorphisms and risk of prostate cancer: a case-control study with an updated meta-analysis

Introduction: Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are the key enzymes of the folate pathway, which involved in the DNA methylation. DNA methylation may affect the stability and integrity of DNA, that supposed to play a pivotal role in carcinogenesis. So, we aimed to investigate the association of MTHFR C677T and MTRR A66G gene polymorphisms with susceptibility to prostate cancer in North Indian population. We also performed meta-analyses of published literatures on these polymorphisms to evaluate their association with prostate cancer. Methods: We genotyped MTHFR C677T and MTRR A66G gene polymorphisms in 147 prostate cancer cases and 147 healthy controls using PCR-RFLP methods. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for risk estimation. For meta-analysis different databases were searched and all statistical analysis were performed using Open Meta-Analyst software. Results: The present case control study revealed that the T allele (OR= 1.67; 95% CI: 0.99-2.84, p= 0.05), CT genotype (OR= 1.92; 95% CI: 1.06-3.48, p= 0.02), and dominant (TT+CT) model (OR= 1.85; 95% CI: 1.05-3.30, p= 0.03) of MTHFR C677T gene polymorphism and G allele (OR= 1.92; 95% CI: 1.35- 2.73, p= 0.0002) of MTRR A66G gene polymorphism were significantly associated with prostate cancer susceptibility. Meta-analyses of MTHFR C677T and MTRR A66G gene polymorphisms showed no significant association between these polymorphisms and prostate cancer risk in overall or in subgroup meta-analysis stratified by ethnicity. Conclusion: MTHFR C677T and MTRR A66G gene polymorphisms seem to play a significant role in prostate cancer susceptibility in North Indian population, while results of meta-analysis revealed no association between MTHFR C677T and MTRR A66G gene polymorphisms and prostate cancer susceptibility.

Interleukin- 10 (IL-10) gene polymorphisms and prostate cancer susceptibility: evidence from a meta-analysis

Prostate cancer is the second most frequent cancer in men. The frequency of the prostate cancer is greatly varies in different populations of the world. Three common polymorphisms in promoter region of interleukin-10 (IL-10) gene viz. -1082 A>G, -819 C>T and -592 C>A are extensively studied in prostate cancer with inconclusive results. So, a meta-analysis was performed to assess the association between these three IL-10 gene polymorphisms and risk of prostate cancer susceptibility. Suitable studies were retrieved by electronic databases search and odds ratios (ORs) with 95% confidence intervals (CIs) were used as association measure. All the statistical analyses were conducted in the Open Meta-Analyst program.In our meta-analysis we included 17 studies (10,718 samples), 11 studies (8,391 samples) and 13 studies (7,801 samples) for -1082 A>G, -819 C>T and -592 C>A polymorphisms respectively. The result of the -592 C>A polymorphism revealed low heterogeneity with no association in the overall analysis (ORAvs.C= 1.05, 95% CI= 0.99-1.12, p= 0.09, I2= 35.89%). In ethnicity based stratified analyses, significant association was found in Caucasian population with prostate cancer using allele contrast model (ORAvs.C= 1.08, 95% CI= 1.01-1.16, p= 0.02, I2= 19.37%), homozygote model (ORAAvs.CC= 1.24, 95% CI= 1.00-1.52, p= 0.04, I2= 0%), and dominant model (ORAA+CAvs.CC= 1.10, 95% CI= 1.00-1.22, p= 0.05, I2= 32.57%). No such results were found in the Asian population. In the other two polymorphisms i.e. -1082 A>G and -819 C>T, no significant association with prostate cancer was observed.In conclusion, results of present meta-analysis suggested that IL-10 -592 C>A polymorphism plays a role in the progression of the prostate cancer in the Caucasian population.