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Abstract
Introduction: Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. This study aimed to elucidate the influence of several GST polymorphisms on colorectal and gastric cancer risk. Patients and methods: GST μ1 (GSTM1), θ1 (GSTT1), π1 (GSTP1), α1 (GSTA1) and μ3 (GSTM3) genotypes were determined in 144 colorectal cancer patients, 98 gastric cancer patients and 329 healthy control individuals. Results: Colorectal cancer: the risk is greater for carriers of the GSTM1 null genotype (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.25–2.91), for carriers of the GSTT1 null genotype (OR = 3.62, 95% CI = 2.34–5.62), and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 4.98, 95% CI = 2.77–9.00). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.31, 95% CI = 0.09–0.88). Among carriers of the GSTP1 Ile/Ile genotype, smoking increases the risk compared with nonsmoking (OR = 2.35, 95% CI = 1.11–4.99). Gastric cancer: the risk is greater for carriers of the GSTT1 null genotype (OR = 2.58, 95% CI = 1.53–4.36) and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 3.32, 95% CI = 1.62–6.77). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.20, 95% CI = 0.02–0.86). Discussion: The GSTT1 null genotype, particularly if it is associated with the GSTM1 null genotype, greatly increases the risk for colorectal and gastric cancers. The GSTP1 104 Val/Val genotype may protect from both malignant tumors. Conclusion: This study indicates that GST polymorphisms, in particular the GSTM1/GSTT1 double-null haplotype, can be considered low-penetrance genes for gastrointestinal cancer.
Acknowledgments
The authors are thankful to Diana Herrero for technical assistance and to James McCue for assistance in language editing. This study was financed in part by Grants SAF 2003–00967 from the Ministerio de Ciencia y Tecnología, FIS 05/1056 from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain and SCSS0506 from Consejería de Sanidad, Junta de Extremadura, Mérida, Spain.