Methionine synthase A2756G polymorphism associated with an increased risk of head and neck cancer

Muhammad Tahir, Aamir Khattak, Haroon Rashid


Background: The 5-methyltetrahydrofolate-homocysteine methyltransferase gene (MTR) encodes the methionine synthase enzyme (OMIM 156570). Methionine synthase synthesizes methionine by re-methylation of homocysteine. A single nucleotide variation MTR-A2756G may affects the function of methionine synthase enzyme, which could lead to the development of head and neck squamous cell carcinoma (HNSCC).

Methods: In current study, 292 HNSCC patients and 324 normal individuals without any history of cancer (control) were enrolled. EDTA whole blood samples of patients and control individuals were collected, and DNA was extracted. All samples were genotyped for MTR-A2756G polymorphism using polymerase chain reaction-restriction fragment length polymorphism. Frequency of polymorphism was compared between HNSCC patients and control individuals. The association of MTR-A2756G polymorphism with risk factors was statistically analysed through multivariate analysis (multiple logistic regression) whereas univariate analysis (chi square) was performed for group comparisons.  

Results: Univariate analysis revealed that the frequency of groups like age, smoking and MTR-A2756G genotype was different in HNC patients and controls (p value <0.05). Multivariate analysis showed that smoking (adjusted OR, 3.7; 95% CI, 2.3-6.0), age groups 41-50 years (adjusted OR, 3.6; 95% CI, .9-6.7) and >60 years (adjusted OR, 3.5; 95% CI, 1.7-7.3), MTR-A2756G genotype (adjusted OR, 2.1; 95% CI, 1.3-3.5) is associated with increased risk of HNSCC.

Conclusions: Our data suggests that the MTR-A2756G polymorphism is associated with the occurrence of HNSCC in Pakistani population while the individuals between 40 to 50 years of age and tobacco smokers are at a greater risk of developing HNSCC.


Methionine synthase, MTR-A2756G, Genetic polymorphism, PCR-RFLP, HNSCC

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