THE HEME-BINDING REGION POLYMORPHISM OF CYTOCHROME P450IA1 (CYPIA1), RATHER THAN THE RSAI POLYMORPHISM OF IIE1 (CYPIIE1), IS ASSOCIATED WITH LUNG-CANCER IN RIO-DE-JANEIRO

Ile-Val polymorphism in exon 7 of cytochrome P450IA1 (CypIA1) and RsaI polymorphism of cytochrome P450IIE1 (CypIIE1) were examined in a case -control study of lung cancer in Rio de Janeiro, Brazil. The Val-conta ining genotype in exon 7 of CypIA1 was found to be associated with lun g cancer in this population (odds ratio, 2.26; 95% confidence interval , 1.14-4.47 for 99 cases versus 108 controls of 123 matched pairs), wh ereas RsaI polymorphism in CypIIE1 was not associated with lung cancer susceptibility. In squamous cell carcinoma, the degree of association of Val-containing genotype was greater in those with fewer pack-years of smoking. The RsaI polymorphism of CypIIE1 has a different distribu tion from the Japanese pattern and is not associated with lung cancer. When we analyzed the association of Ile-Val polymorphism to MspI poly morphism of CypIA1, the Val/Val homozygote was found only in the subpo pulation with the MspI site-present homozygote. The apparent lack of a ssociation of CypIA1 MspI polymorphism with lung cancer in this area r eported in our previous study and the results of the present study ind icate that the ''true'' responsible site for lung cancer susceptibilit y should be the Ile-Val polymorphism in the catalytic site of CypIA1.