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Carcinogenesis Advance Access published online on October 4, 2007
Carcinogenesis, doi:10.1093/carcin/bgm222
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Polymorphisms of GSTP1 and GSTT1, but not of CYP2A6, CYP2E1 or GSTM1, modify the risk for esophageal cancer in a Western population

A. Rossini1, D. C. M. Rapozo1, S. C. Soares Lima1, D. P. Guimarães2, M.A. Ferreira2, R. Teixeira2, C. D. P. Kruel3, S. G. S. Barros4, N. A. Andreollo5, R. Acatauassú6, H. J. Matos7, R. M. Albano1 and L. F. Ribeiro Pinto1,2,8

1 Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro
2 Serviço de Endoscopia Digestiva e Serviço de Pesquisa Clínica e Translacional, Coordenação de Pesquisa, INCA
3 Departamento de Cirurgia Gástrica, FCM-HCPA, Universidade Federal do Rio Grande do Sul
4 Serviço de Gastroenterologia, HCPA, Universidade Federal do Rio Grande do Sul
5 Departamento de Cirurgia e Gastrocentro, FCM-UNICAMP
6 Disciplina de Gastroenterologia, FCM-HUPE, Universidade do Estado do Rio de Janeiro
7 Departamento de Tecnologia da Informação e Educação em Saúde, FCM, Universidade do Estado do Rio de Janeiro, RJ, Brasil

8 To whom correspondence should be addressed at: Av. 28 Setembro, 87, fundos, 4o andar, Vila Isabel, Rio de Janeiro, RJ, Brasil. CEP: 20551-013 Emails: frpinto{at}oi.com.br / fpinto{at}uerj.br / lfrpinto{at}inca.gov.br

Esophageal cancer is among the most common and fatal tumors in the World. Eighty percent of esophageal tumors are squamous cell carcinoma (ESCC). Brazil is one of the high incidence areas in the West, where tobacco and alcohol consumption have been associated with ESCC. However, polymorphisms in xenobiotic metabolizing genes may also contribute to the risk. Therefore, in this study we analysed the risk of ESCC associated with tobacco and alcohol consumption, and with polymorphisms of CYP2A6 (CYP2A6*2), CYP2E1 (CYP2E1*5B, CYP2E1*6), GSTP1 (Ile105Val), GSTM1 and GSTT1 null genotypes in 126 cases and 252 age- and gender-matched controls. Data on the amount, length and type of tobacco and alcohol consumed was collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analysed either by PCR-multiplex (GSTM1 and T1), PCR-RFLP (CYP2E1*5B and *6 and GSTP1 Ile105Val), or allele-specific PCR amplification (CYP2A6*2). Risks were evaluated by multivariate conditional regression analysis. As expected, tobacco (OR = 6.71; CI 3.08-14.63) and alcohol (OR = 16.98; CI 7.8-36.98) consumption, independently or together (OR = 26.91; CI 13.39-54.05) were risk factors. GSTP1 Ile105Val polymorphism was an independent risk factor (OR = 2.12; CI 1.37-3.29), whereas GSTT1 wild type was an independent protective factor for ESCC (OR = 0.37; CI 0.16-0.79). There was around 80% statistical power to detect both results. There was no risk associated with CYP2A6, CYP2E1 and GSTM1 polymorphisms. In conclusion, this study suggests an opposite role of GSTP1 and GSTT1 polymorphisms for the risk for ESCC.

Key Words: esophagus • cancer • polymorphism • CYP • GST

Received June 18, 2007; revised August 22, 2007; accepted September 7, 2007.


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