There were interactions between lower survival and CBS 844ins68 (P=0.005); age ≥ 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk.
The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase), involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC).
None of the polymorphisms showed any significant impact on HNSCC risk by genotype alone, but we found interactions between drinking habit and MTHFR C667T (P = 0.04), MTRA2756G (P = 0.04) and MTRR A66G (P = 0.03) polymorphisms.
In conclusion, our data provide evidence that support the association between the MTRA2756G and MTRR G66A polymorphisms and SCCHN risk and that these two polymorphisms may have a joint effect on risk of SCCHN.