RESUMO
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-containing genotype in exon 7 of CypIA1 was found to be associated with lung 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), whereas 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 distribution from the Japanese pattern and is not associated with lung cancer. When we analyzed the association of Ile-Val polymorphism to MspI polymorphism of CypIA1, the Val/Val homozygote was found only in the subpopulation with the MspI site-present homozygote. The apparent lack of association of CypIA1 MspI polymorphism with lung cancer in this area reported in our previous study and the results of the present study indicate that the "true" responsible site for lung cancer susceptibility should be the Ile-Val polymorphism in the catalytic site of CypIA1.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Desoxirribonucleases de Sítio Específico do Tipo II/genética , Heme/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Oxirredutases N-Desmetilantes/genética , Polimorfismo Genético/genética , Brasil , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Citocromo P-450 CYP2E1 , Sistema Enzimático do Citocromo P-450/metabolismo , Desoxirribonuclease HpaII , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Etnicidade , Éxons/genética , Feminino , Ligação Genética/genética , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Oxirredutases N-Desmetilantes/metabolismo , Ligação Proteica/genética , Fumar/genética , Valina/genéticaRESUMO
Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYP1A1, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.