The role of polymorphic genes in genetic susceptibility to xenobiotics
Breskvar, Katja ; Dolžan, Vita ; Rudolf, Zvonimir
There is considerable evidence that initiation of lung carcinoma in man is a consequence of activation of environmental carcinogens by cytochrome P450 dependent monooxygenase system. The risk of lung ...cancer was associated with the ability of individuals to metabolize xenobiotics. Among others two polymorphic genes for P450 CYP2D6, responsible for metabolism of debrisoquine and other drugs and CYP1A1, involved in metabolism of polycyclic arylhydrocarbons, appear to be markers of susceptibility for lung cancer. A genotyping approach was used in clinical and polution studies aimed to ascertain the risk for certain cancer diseases in order to determine the frequencies of polymorphic alleles of CYP2D6 and CYP1A1 in healthy individualsand lung cancer patients. In healthy population of 107 Slovene individuals 6.5 percent were indentified as poor metabolizers of debrisoquine,64 percent as extensive metabolizers and 29.5 percent as extensive-heterozygous metabolizers. These results correlate well with the results obtained by phenotyping other Caucasian populations. In the group of 200 cancer patients lower incidence of poor metabolizer individuals was observed (2.5 percent) when compared with healthy population. CYP1A1 polymorphism w determined in 50 healthy individuals and in 51 lung cancer patients. No significant differencies in frequencies of the analysed polymorphic CYP1A1 markers were observed in both groups of individuals.
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