Diet, genetic susceptibility and carcinogenesis.
At least six types of gene-environment interactions (GEI) have been proposed (Kouhry and Wagener, 1993). In the first type, neither the environmental exposure (EE) nor the genetic risk factor (GRF) have any effect by themselves, but interaction between them causes disease. This is the case of phenylalanine exposure and the phenylketonuria genotype. Type 2 is a situation in which the GRF has no effect on disease in the absence of exposure, but exacerbates the effects of the latter. This is the most important type of GEI in relation to metabolic susceptibility genes and human carcinogenesis. The third type is the converse of the second (EE is ineffective per se, but enhances the effect of GRF). Type 4 occurs when both FE and GRF increase the risk for disease, but the combination is interactive or synergistic: an example is the interaction between Xeroderma Pigmentosum and LWV radiation. Types 5 and 6, according to the classification proposed by Kouhry, refer to cases in which the GRF is protective. The model of GEI that is emerging as the most important in chemical carcinogenesis refers to metabolic susceptibility genes. The general population can be divided into subgroups depending on their susceptibility to the action of carcinogens, based on their ability to metabolize such compounds to electrophilic, reactive metabolites (which form adducts with DNA), or, respectively, electrophobic metabolites that are excreted. The present contribution is a short review of the relevant literature, with particular emphasis on some polymorphisms involved in dietary exposures. In addition, the practical implications of genetic testing in this field are discussed.
Vineis
P
P
Unit of Cancer Epidemiology, University of Torino and CPO-Piemonte, Torino, Italy. paolo.vineis@unito.it
D002274:Carcinogens, Environmental / Q000378:metabolism*; D004032:Diet; D004781:Environmental Exposure; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic
D002274:Carcinogens, Environmental