ORIGINAL ARTICLE SUMMARY Objective: To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to fnd the association of the poly- morphism with the risk factors and clinical and histopathological characteristics. Metho- ds: Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. Results: Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA geno- types were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more ofen found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). Conclusion: Te presence of MTHFD1 G1948A polymorphism as- sociated with smoking and alcoholism raises the head and neck cancer risk. Keywords: Polymorphism, genetic; head and neck neoplasms; alcoholism; smoking; me- thylenetetrahydrofolate dehydrogenase (NADP). Study conducted at the Unit of Research in Genetics and Molecular Biology (UPGEM), Medical College of São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil Submitted on: 11/3/2010 Approved on: 1/25/2011 Funding Support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Research Support Foundation, State of São Paulo] and Conselho Nacional de Desenvolvimento Científco e Tecnológico (CNPq) [National Board of Scientifc and Technological Development]. Correspondence to: Eny Maria Goloni-Bertollo Unidade de Pesquisa em Genética e Biologia Molecular – UPGEM da Faculdade de Medicina de São José do Rio Preto – FAMERP Av. Brigadeiro Faria Lima, 5416 CEP: 15090-000 São José do Rio Preto – SP eny.goloni@famerp.br Confict of interest: None. Head and neck carcinogenesis: impact of MTHFD1 G1958A polymorphism LIDIA MARIA REBOLHO BATISTA DA SILVA 1 , JÉSSIKA NUNES GOMES DA SILVA 2 , ANA LÍVIA SILVA GALBIATTI 1 , MAYSA SUCCI 3 , MARIANGELA TORREGLOSA RUIZ 4 , LUIZ SÉRGIO RAPOSO 5 , JOSÉ VÍCTOR MANIGLIA 6 , ÉRIKA CRISTINA PAVARINO-BERTELLI 7 , ENY MARIA GOLONI-BERTOLLO 8 1 M.Sc. in Sciences of Health, Ph.D. Student at the Unit of Research in Genetics and Molecular Biology - UPGEM, Medical College of São José do Rio Preto - FAMERP, São José do Rio Preto, SP, Brazil 2 B.Sc. in Speech, Language and Hearing Sciences, Medical Student, FAMERP, São José do Rio Preto, SP, Brazil 3 M.Sc. in Sciences of Health, Ph.D. Student at the UPGEM/ FAMERP, São José do Rio Preto, SP, Brazil 4 Biological Sciences Student, Universidade Estadual Paulista Júlio de Mesquita Filho - Unesp, São José do Rio Preto, SP, Brazil 5 Ph.D in Sciences of Health, FAMERP, São José do Rio Preto, SP, Brazil 6 M.Sc. in Sciences of Health, Professor at the Department of Otorhinolaryngology and Head and Neck Surgery, FAMERP, São José do Rio Preto, SP, Brazil 7 Assistant Professor, Lecturer at the Department of Otorhinolaryngology and Head and Neck Surgery, FAMERP, São José do Rio Preto, SP, Brazil 8 Assistant Professor, Lecturer at the Department of Molecular Biology, FAMERP, São José do Rio Preto, SP, Brazil 9 Lecturer in Human and Medical Genetics – Professor at Department of Molecular Biology, FAMERP, São José do Rio Preto, SP, Brazil 188