Diet, genetic susceptibility and carcinogenesis
Unit of Cancer Epidemiology, University of Torino and CPO-Piemonte, via Santena 7 10126 Torino, Italy
Short Title: Diet, genetics and carcinogenesis
Keywords : Diet, genetic susceptibility, carcinogenesis, metabolic polymorphisms, DNA repair
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 EE and GRF increase the
risk for disease, but the combination is interactive or synergistic : an
example is the interaction between Xeroderma Pigmentosum and UV 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.
* Correspondence: Fax: +39 011 6706692, E-mail: Paolo.vineis@Unito.it
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