Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk

Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age >= 49 years (P < 0.001), male gender (P = 0.03), tobacco habit (P < 0.001), MTHFR 1298AC/CC (P = 0.028), MTR 2756AG/GG (P = 0.010) and RFC1 80AG/GG (P = 0.015) genotypes were associated with an increased risk of HNSCC. 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. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P = 0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.