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Carcinogenesis Advance Access originally published online on October 4, 2007
Carcinogenesis 2007 28(12):2537-2542; 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,*

1 Departamento de Bioquímica, IBRAG, Universidade do Estado do Rio de Janeiro, RJ 20551-013, Brasil
2 Serviço de Endoscopia Digestiva e Serviço de Pesquisa Clínica e Translacional, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de janeiro, CEP: 20231-050, Brasil
3 Departamento de Cirurgia Gástrica, Faculdade de Ciências Médicas-Hospital da Clínicas de Porto Alegre, Rio Grande do Sul, CEP 90035-003, Brasil
4 Serviço de Gastroenterologia, Hospital da Clínicas de Porto Alegre, Rio Grande do Sul, CEP 90035-003, Brasil
5 Departamento de Cirurgia e Gastrocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, CEP 13083-970, Brasil
6 Disciplina de Gastroenterologia, FCM-HUPE, Universidade do Estado do Rio de Janeiro 20551-013
7 Departamento de Tecnologia da Informação e Educação em Saúde, FCM, Universidade do Estado do Rio de Janeiro, RJ 20551-013, Brasil

* To whom correspondence should be addressed. Tel: +55 21 25876428; Fax: +55 21 25876136; Email: frpinto{at}oi.com.br

Esophageal cancer is among the most common and fatal tumors in the world. Eighty percent of esophageal tumors are esophageal 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 analyzed 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 were collected, and DNA was extracted from blood lymphocytes from all individuals. Polymorphisms were analyzed by polymerase chain reaction (PCR)–multiplex (GSTM1 and T1), PCR–Restriction Fragment Length Polymorphism (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 [odds ratio (OR) = 6.71, 95% confidence interval (95% 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 ~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.

Abbreviations: CYP, cytochrome P450; 95% CI, 95% confidence interval; ESCC, esophageal squamous cell carcinoma; GST, glutathione S-transferase; OR, odds ratio; PCR, polymerase chain reaction

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


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