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GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

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World Journal of Gastroenterology 2004年第23期10卷 3389-3393页

作者： Ahmed Abbas Karine Delvinquière Mathilde Lechevrel Pierre Lebailly pascal gauduchon Guy Launoy Fran ois Sichel GRECAN-EA1772 UFR des Sciences Pharmaceutiques Université de Caen Basse-Normandie et Centre Francois BaclesseAvenue du Général Harris14076 Caen cedex 05France GRECAN-EA1772 Université de Caen Basse-Normandie et Registre des Tumeurs Digestives du Calvados UFR de MédecineAvenue de la C te de Nacre14032 Caen cedexFrance

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological *** frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco *** ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

关键词： Acyltransferases Adenocarcinoma Adult Aged Aged, 80 and over Carcinoma, Squamous Cell Case-Control Studies Cytochrome P-450 CYP1A1 Esophageal Neoplasms Female France Genetic Predisposition to Disease Genotype Glutathione Transferase Humans Male Middle Aged Polymorphism, Genetic Research Support, Non-U.S. Gov't Risk Factors

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