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Folate, alcohol, and aldehyde dehydrogenase 2 polymorphism and the risk of oral and pharyngeal cancer in Japanese

Matsuo, Keitaroa,d; Rossi, Martae,f; Negri, Evae; Oze, Isaoa; Hosono, Satoyoa; Ito, Hidemia; Watanabe, Mikia; Yatabe, Yasushib; Hasegawa, Yasuhisac; Tanaka, Hideoa,d; Tajima, Kazuoa; La Vecchia, Carloe,f

European Journal of Cancer Prevention: March 2012 - Volume 21 - Issue 2 - p 193–198
doi: 10.1097/CEJ.0b013e32834c9be5
Research Papers: Head and Neck cancer

Folate consumption is inversely associated with the risk of oral and pharyngeal cancer (OPC) and potentially interacts with alcohol drinking in the risk of OPC. Aldehyde dehydrogenase 2 (ALDH2) gene polymorphism is known to interact with alcohol consumption. The aim of this study was to investigate potential interaction between folate, alcohol drinking, and ALDH2 polymorphism in the risk of OPC in a Japanese population. The study group comprised 409 head and neck cancer cases and 1227 age-matched and sex-matched noncancer controls; of these, 251 cases and 759 controls were evaluated for ALDH rs671 polymorphism. Associations were assessed by odds ratios and 95% confidence intervals in multiple logistic regression models. We observed an inverse association between folate consumption and OPC risk. The odds ratio for high folate intake was 0.53 (95% confidence interval: 0.36–0.77) relative to low intake (P trend=0.003). This association was consistent across strata of sex, age, smoking, and ALDH2 genotypes. Interaction between folate consumption, drinking, and ALDH2 genotype was remarkable (three-way interaction, P<0.001). We observed significant interaction among folate, drinking, and ALDH2 genotype in the Japanese population.

aDivision of Epidemiology and Prevention

bDepartment of Pathology and Molecular Diagnostics

cDepartment of Head/Neck Surgery, Aichi Cancer Center Hospital

dDepartment of Epidemiology, Nagoya University Graduate School of Medicene, Nagoya, Japan

eDepartment of Epidemiology Instituto di Ricerche Farmacologiche ‘Mario Negri’

fDepartment of Occupational Health, Universitá degli Studi di Milan, Milano, Italy

Correspondence to Dr Keitaro Matsuo, MD, PhD, MSc, 1–1 Kanokoden, Chikusa-ku, Nagoya-city, Aichi 464–8681, Japan Tel: +81 52 762 8111; fax: +81 52 763 5233; e-mail:

Received May 31, 2011

Accepted August 26, 2011

© 2012 Lippincott Williams & Wilkins, Inc.