J Cancer 2017; 8(2):266-277. doi:10.7150/jca.17379
Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies
1. The Key Laboratory of Pharmacology and Medical Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China;
2. The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang 471023, Henan, China;
3. Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
* These authors contributed equally to this work.
Wang P, Li S, Wang M, He J, Xi S. Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies. J Cancer 2017; 8(2):266-277. doi:10.7150/jca.17379. Available from http://www.jcancer.org/v08p0266.htm
Methionine synthase reductase (MTRR) is a key regulatory enzyme involved in the folate metabolic pathway. Previous studies investigating the association of MTRR A66G polymorphism with cancer susceptibility reported inconclusive results. We performed the current meta-analysis to obtain a more precise estimation of the possible association. Published literatures were identified from PubMed, Embase and CBM databases up to October 2016. The strength of the association between the MTRR A66G polymorphism and cancer susceptibility was assessed using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Eighty five published studies with 32,272 cases and 37,427 controls were included in this meta-analysis. Pooled results indicated that the MTRR A66G polymorphism was associated with an increased overall cancer risk (homozygous model: OR = 1.08, 95% CI = 1.02-1.15, P = 0.009; recessive model: OR = 1.06, 95% CI = 1.00-1.12, P < 0.001 and allele comparison: OR = 1.03, 95% CI = 1.00-1.06, P < 0.001). Stratification analysis further indicated significant associations in head and neck cancer, Caucasians, Africans, and high quality studies. However, to avoid the “false-positive report”, the significant findings were assessed by the false-positive report probability (FPRP) test. Interestingly, the results of FPRP test revealed that the increased risk for MTRR A66G polymorphism among Africans need further validation due to the high probabilities of false-positive results. This meta-analysis suggests that the MTRR A66G polymorphism is associated with significantly increased cancer risk, a finding that needs to be confirmed in single large studies.
Keywords: Methionine synthase reductase (MTRR), polymorphism, susceptibility, meta-analysis.