Association between MPO-463G > A polymorphism and cancer risk: evidence from 60 case-control studies

BACKGROUND Though a number of studies have been conducted to explore the association between myeloperoxidase (MPO)-463G > A polymorphism and cancer risk, the results remain inconsistent. Therefore, we performed a meta-analysis to derive a more systematic estimation of this relationship. METHOD Relevant studies were searched by PubMed, EMBASE, CNKI, Google Scholar, Ovid, and Cochrane library prior to December 2015. The strength of the association between MPO-463G > A polymorphism and cancer risk was estimated by odds ratios (OR) with 95% confidence interval (95%CI). Cumulative analysis was used to evaluate the stability of results through time. RESULTS The current analysis consisted of 16,858 cases and 21,756 controls from 60 studies. Pooled results showed that MPO-463G > A polymorphism were associated with the overall decreased cancer susceptibility in all the genetic models included in this study (additive model: OR = 0.84, 95%CI = 0.76-0.94; allele genetic model: OR = 0.90, 95%CI = 0.840-0.954; recessive genetic model: OR = 0.89, 95%CI = 0.83-0.95). However, in the stratified analysis of cancer type, the significant results were only found in lung cancer (dominant model: OR = 0.93, 95%CI = 0.87-0.99) and digestive system cancer groups (dominant model: OR = 0.67 0.53-0.84; allele frequency model = 0.71, 95%CI = 0.57-0.87), but not in the blood system cancer or breast cancer group. When we further stratified the digestive system cancer group into digestive tract and digestive gland cancer groups, results showed a significant association between allele A of MPO-463G > A and digestive gland cancer in all the genetic models (allele frequency model: OR = 0.63, 95%CI = 0.40-0.99; additive model: OR = 0.41, 95%CI = 0.23-0.73; recessive model: OR = 0.51, 95%CI = 0.29-0.89; dominant model: OR = 0.58, 95%CI = 0.35-0.96), digestive tract cancers in allele frequency model (OR = 0.75, 95%CI = 0.59-0.95), and dominant model (OR = 0.72, 95%CI = 0.56-0.92). When stratified by ethnicity, results demonstrated that the genotype A might be a protect factor for both Caucasians and Asians. In group analysis according to source of controls, significant results were found in population from hospital in all the genetic models. In cumulative analysis, result of allele contrast showed a declining trend and increasingly narrower 95% overall, while the inclination toward non-significant association with lung cancer risk. CONCLUSIONS This meta-analysis suggested that MPO-463G > A polymorphism was associated with the overall reduced cancer susceptibility significantly. It might be a more reliable predictor of digestive system cancer instead of lung cancer, blood system cancer, and breast cancer. In cumulative analysis, the stable trend indicated that evidence was sufficient to show the association between MPO-463G > A polymorphism and cancer risk.