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Contribution à l'étude des mécanismes de l'interaction alcool-tabac dans l'étiologie du cancer de l'oesophage

Abstract : The molecular basis of the interaction between alcohol in the aetiopathogenesis of esophageal squamous cell carcinoma remains unclear. One hypothesis is that alcohol intake could modify the expression of enzymes metabolizing tobacco carcinogens in liver and esophageal mucosa. First, we tested the hypothesis that different alcoholic beverages could differentially induce expression of liver and esophageal cytochromes P450 in rats treated by various alcohols (wine, cider, beer, whisky, calvados brandy-farm produced or commercial, ethanol alone) and then exposed to N-methylbenzylnitrosamine. The data show that induction of CYP2E1 with acute alcohol treatment was predominantly determined by the ethanol content of the beverage and that in rat this induction is seen in liver but not in esophagus. The type of beverage does not affect cyrochromes expression and methylation adducts in liver and esophagus. Second, from a study realized on biopsies of non neoplastic mucosa, we support the hypothesis that human oesophageal mucosa can activate different tobacco carcinogens. The presence of CYP2E1, CYP1A1/2 and CYP3A3/4 was confirmed in this tissu. We have related the level of their expression to epidemiological data concerning tobacco and alcohol consumption ; however no significant increase was seen. The cell proliferation could contribute to carcinogenesis process. The study of expression of cell proliferation marker (Ki67) and of p53 protein in non neoplastic mucosa near the tumor (12 cases) and normal mucosa (22) from healthy volunteers shows an important cell proliferation accompagnied with p53 expression in oesophagitis area. The appearance of chronic oesophagitis was related significantly to the level of hot alcohol brandies intake. These data suggest that carcinogenesis process could appear early in chronic inflammatory areas of esophageal mucosa
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Mathilde Lechevrel. Contribution à l'étude des mécanismes de l'interaction alcool-tabac dans l'étiologie du cancer de l'oesophage. Sciences agricoles. Université Paul Verlaine - Metz, 1997. Français. ⟨NNT : 1997METZ039S⟩. ⟨tel-01777222⟩



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