Polymorphisms of methionine synthase and methionine synthase reductase and risk of squamous cell carcinoma of the head and neck: a case-control analysis.
Although tobacco and alcohol use are the major risk factors, folate deficiency has been implicated in the risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that polymorphisms of methionine synthase (MTR) and methionine synthase reductase (MTRR) in the folate metabolic pathway are associated with SCCHN risk. In a hospital-based case-control study of 721 SCCHN cases and 1,234 controls of non-Hispanic Whites, frequency matched by age, sex, and smoking status, we genotyped the MTR A2756G and MTRR G66A polymorphisms. We found that the MTR variant AG and AG/GG genotypes were associated with a significantly increased SCCHN risk [adjusted odd ratio (OR), 1.31; 95% confidence interval (95% CI), 1.07-1.60 for AG and OR, 1.28; 95% CI, 1.05-1.56 for AG/GG] compared with the AA genotype. In contrast, the MTRR variant AA genotype was associated with a significantly decreased SCCHN risk (OR, 0.68; 95% CI, 0.52-0.90) compared with the 66GG genotype. When the two polymorphisms were evaluated together by the number of risk alleles, the SCCHN risk was significantly increased in a dose-dependent manner (P(trend) = 0.002). The risk of SCCHN was 1.47 (95% CI, 1.08-1.99) for one risk allele, 1.67 (95% CI, 1.23-2.27) for two risk alleles, and 1.74 (95% CI, 1.18-2.54) for three or four risk alleles compared with the wild-type (0 risk allele) genotype. In conclusion, our data provide evidence that support the association between the MTR A2756G and MTRR G66A polymorphisms and SCCHN risk and that these two polymorphisms may have a joint effect on risk of SCCHN.
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- White People
- Texas
- Smoking
- Risk Factors
- Polymorphism, Genetic
- Polymerase Chain Reaction
- Middle Aged
- Male
- Logistic Models
- Interviews as Topic
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- White People
- Texas
- Smoking
- Risk Factors
- Polymorphism, Genetic
- Polymerase Chain Reaction
- Middle Aged
- Male
- Logistic Models
- Interviews as Topic