Pooled results indicated that the <i>MTRR</i> A66G polymorphism was associated with an increased overall cancer risk (homozygous model: OR = 1.08, 95% CI = 1.02-1.15, <i>P</i> = 0.009; recessive model: OR = 1.06, 95% CI = 1.00-1.12, <i>P</i> < 0.001 and allele comparison: OR = 1.03, 95% CI = 1.00-1.06, <i>P</i> < 0.001).
The MTRRA66G (rs1801394) polymorphism is found to be associated with decreased enzyme affinity for MTR, the gene that encodes MS, and has been widely investigated for cancer risk, including leukemia.
For LINE-1, the association tended to be stronger among individuals with a family history of cancer (OR = 3.1, 95% CI = 1.4-7.0, p for interaction = 0.01), current alcohol drinkers (OR = 1.9, 95% CI = 1.0-3.6, p for interaction = 0.05), current smokers (OR = 2.3, 95% CI = 1.1-4.6, p for interaction = 0.02), those who rarely or never consumed fruit (OR = 3.1, 95% CI = 1.2-8.1, p for interaction = 0.03), CC carriers for the MTRR Ex5+123C>T polymorphism (OR = 2.3, 95% CI = 1.2-4.4, p for interaction = 0.01) and TT carriers for the MTRR Ex15+572T>C polymorphism (OR = 1.7, 95% CI = 1.0-2.8, p for interaction = 0.06).
Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) play an essential role in both DNA synthesis and methylation and polymorphisms in the MTHFR gene, 677C>T, 1298A>C and the MTRR gene, 66A>G, are associated with several types of malignancy.