Alcohol metabolizing gene polymorphisms and their relationship with oral cancer risk and clinicopathological features

Author(s): J.T. Takamori, M. Santos, G. T. Peterle, L. Rossi, O. A. Curioni, D. Gazito, L. L. Maia, I. D. Louro, M. M. de Oliveira, J. G. dos Santos, R. A. Moyses, P. M. Cury, T. N. Toporcov, J. L. Kanda, A. M. A. da Silva, M. B. de Carvalho

Oral cancer incidence is higher in individuals between the fifth and seventh decades of life, but some studies indicate a decreasing age trend. From the epidemiological point of view, alcohol consumption is associated with the emergence of oral cancer by interfering with mechanisms of DNA synthesis and repair. From a genetic standpoint, variant alleles in genes encoding the enzymes of alcohol (CYP2E1 and ADH) and acetaldehyde (ALDH2) metabolism may play an important role in the genesis of oral cancer. This study aimed to assess the relation of polymorphisms ADH1B (rs1229984 and rs2066702), ADH1C (rs698), ALDH2 (rs671) and CYP2E1 96bp insertion and the risk of squamous cell carcinoma of the mouth floor, as well as its clinicopathological and prognostic characteristics in relation to alcohol consumption. Our sample group was made of 301 patients, with 159 controls without a previous history of cancer and 142 patients with oral cancer. Genomic DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP. Our results suggest that the presence of ALDH2 Lys504 allele and 96bp insertion CYP2E1 were significantly associated with oral cancer risk. ADH1C gene Ile350 allele was associated with the presence of positive lymph nodes, and lymphatic invasion was related to the presence of polymorphic alleles ADH1B*1, ADH1C Ile350 and ALDH2 Lys504. In conclusion, these results reveal potential markers of oral cancer risk and behavior

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