Abstract
The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk.
Highlights
Folate and significantly reduced activity of the MTHFR enzyme[18,19,20]
A total of nine studies including 2,092 cases and 4,954 controls were included for the C677T polymorphism[24,25,26,27,28,29,30,31,32], seven studies bearing 732 cases and 2,841 controls for the A1298C polymorphism[24,26,27,28,29,30,32,33]
MTHFR plays an important role in the regulation of DNA synthesis, methylation, and repair
Summary
Folate and significantly reduced activity of the MTHFR enzyme[18,19,20]. The hypomethylation of DNA may result in activation and increased expression of proto-oncogenes, contributing to an increased prevalence of cancer[23]. Individual susceptibility to cancer may be modified by some functional polymorphisms of MTHFR gene through the alteration of DNA synthesis and methylation. There have been several studies investigating the relationship between MTHFR C677T and A1298C genetic polymorphisms and MM susceptibility, but the published results are inconsistent, which may be attributed to the relatively small sample size and different ethnic background in each study[24,25]. A meta-analysis was carried out to comprehensively evaluate the association of MTHFR C677T or A1298C polymorphisms with MM risk
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