Lung cancer risk and CYP1A1 genotype in African Americans.

The role of CYP1A1 genotype in lung cancer risk was assessed in African Americans through a case control study. The complete CYP1A1 genotype, including the frequency of all three polymorphisms (Msp1 [CYP1A12], exon 7 [CYP1A13] and African American specific [CYP1A1*4]) was determined by PCR on 307 controls and 105 cases of lung cancer among African Americans. We have confirmed our earlier observation of a significant increased risk (odds ratio = 2.8, 95% CI = 1.3-6.5) for lung adenocarcinoma among people with the *4 polymorphism, although we did not observe any association of this polymorphism with overall lung cancer risk. As previously reported, we found that lung adenocarcinoma patients with the *4 RFLP smoked significantly less than patients without this polymorphism, suggesting an important role in cancer risk of low exposure levels to cigarette smoke in subjects carrying susceptibility polymorphisms. There was no association with the other two polymorphisms and lung cancer in this population. When we examined lung cancer risk as a function of composite genotype, taking into account all three polymorphisms simultaneously in each subject, our preliminary data suggested an association of one rare genotype (homozygous Msp1, heterozygous exon 7 or *2/23) with overall lung cancer risk (OR = 8.4, 95% CI = 1.6-43.2).