Methylenetetrahydrofolate reductase polymorphisms and risk of squamous cell carcinoma of the head and neck: A case‐control analysis

Abstract

Folate deficiency is implicated in cancer risk that may be modulated by a genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene in folate metabolism. We hypothesized that genetic variants in MTHFR are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We genotyped 3 MTHFR polymorphisms (C677T, A1298C and G1793A) and estimated their haplotypes in a hospital-based case-control study of 537 SCCHN cases and 545 cancer-free controls. The controls were frequency-matched to the cases by age (6 5 years), sex, ethnicity and smoking status. We found that the MTHFR 1298AC/ CC genotypes were associated with an approximately 35% reduction in risk of SCCHN (adjusted odds ratio = 0.65; 95% CI = 0.51-0.82) compared to the AA genotype. The MTHFR 677CT and 1793GA/AA genotypes were associated with nonsignificant increased risk of SCCHN compared to the 677CC and 1793GG genotypes, respectively. We estimated that there were 8 haplotypes and 16 haplotype genotypes based on these 3 variants. When we used the haplotypes and assumed that the 677T, 1298A and 1793A alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.85 (1.3-2.5) for any 2 risk alleles and 1.93 (1.4-2.7) for any 3 risk alleles. These results suggest that all 3 MTHFR polymorphisms may play a role in the susceptibility to SCCHN among non-Hispanic whites. Future studies should incorporate detailed data on alcohol consumption, dietary folate intake and related serologic measurements. ' 2005 Wiley-Liss, Inc.

Sex Differences in Risk of Lung Cancer Associated with Methylene-tetrahydrofolate Reductase Polymorphisms

“…We found no increase in risk associated with the variant genotypes, a result consistent with our previous study of squamous cell carcinoma of the head and neck (49). The newly identified G1793A located in exon 11 at codon 594, causes an arginine-to-glutamine change (28).…”

Global DNA Methylation Level in Whole Blood as a Biomarker in Head and Neck Squamous Cell Carcinoma

“…Given the relationship between MTHFR function and levels of circulating folate (in the form of 5-methyl-THF), this is to be expected, particularly because various MTHFR polymorphisms have been implicated as risk factors for HNSCC (49). Preliminary analysis of our data has suggested that MTHFR 677genotype is not an independent risk factor for HNSCC, but its influence on hypomethylation may suggest the possibility for effect modification by this or other factors.…”

Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: A case–control analysis

“…Univariate and multivariate unconditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for assessing risk of lung cancer. The putative risk genotypes and alleles were determined, if their frequencies were higher in the lung cancer patients than in the controls [18]. Because there was no prior information about the effects of these SNPs on lung cancer risk, we used Akaike's information criterion (AIC) to select the best genetic-effect model for each SNP.…”