CYTOCHROMES P4502E1 AND P4501A1 GENOTYPES AND SUSCEPTIBILITY TO CIRRHOSIS OR UPPER AERODIGESTIVE TRACT CANCER IN ALCOHOLIC CAUCASIANS

Genetic polymorphisms of various cytochromes P450 have recently been d escribed and could be implicated in the individual susceptibility of a lcoholics to ethanol-related diseases. RsaI and DraI polymorphisms of CYP2E1 and MspI polymorphism of CYP1A1 were studied in 260 controls an d 511 alcoholic patients, without any clinical symptoms (n = 202) or w ith various ethanol-related diseases (n = 309), such as liver cirrhosi s (n = 110), esophageal cancer (n = 62), upper aerodigestive tract can cer (n = 96), and other miscellaneous diseases (n = 41). Frequencies o f the mutated alleles wore found to be 2.5% (RsaI), 7.9% (DraI), and 8 .7% (MspI) in controls; 4%, 14.1%, and 12% in alcoholics without clini cal symptoms; and 3.1%, 12.5%, and 11.2% in alcoholics with ethanol-re lated diseases, The only significant difference was found in the DraI polymorphism, whose frequency was enhanced in alcoholics with (p < 0.0 5) or without ethanol-related diseases (p < 0.01) when compared with c ontrols. No differences were found between alcoholics without clinical symptoms and alcoholics with cirrhosis, esophageal cancer, or upper a erodigestive tract cancer. However, in liver cirrhosis and in ethanol- related cancers, the rare DraI-C allele was three times less frequent in patients under the age of 45 than in older patients, suggesting a p rotective role for this allele. In conclusion, our data indicate that the aforementioned mutations do not play a critical role in the develo pment of cirrhosis, esophageal cancer, or upper aerodigestive tract ca ncers in Caucasians.