Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

Abstract

Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a populationbased case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sexmatched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 exon 7 Ile 462 Val and CYP1B1 Leu 432 Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 MspI or CYP1B1 Leu 432 Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the Ile/Val genotype at CYP1A1 exon 7 locus were at decreased risk of having lung cancer compared to those with the Ile/Ile genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% CI 0.19-0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

“…A population-based study (52) found that Caucasians but not African Americans with IIe/Val (CYP1A1*2C) genotype were at a lower risk of developing lung cancer than those with lle/lle (*1/*1) genotype, after adjusting for age at diagnosis, sex, years of smoking and family history of cancer. A recent study (53) (105)Val.…”

Variability in Small Airway Epithelial Gene Expression Among Normal Smokers

“…For example, cytochromes P450 are critical to metabolism of the xenobiotics in tobacco smoke and CYP1B1 in particular has been implicated in the oxidation of benzopyrene 35,36 . Polymorphisms of CYP1B1 have previously been implicated in susceptibility to various types of cancer including lung cancer 37,38 . Expression of MUC5AC has also been investigated in airway epithelial cells and shown to be induced by inflammatory stimuli 39 .…”

Association Between the CYP1B1 Polymorphisms and Lung Cancer Risk

“…Another 26 articles among these publications were excluded because they were review articles, case reports, and other polymorphisms of CYP1B1. In addition, the study of Cote et al 13 was excluded because patients were included in the study of Cote et al 17 As summarized in Table 1, 12 publications with 22 case-control studies were included in the meta-analysis, including 2881 cases and 3653 controls for CYP1B1 Leu432-Val polymorphism (from 13 studies), 3009 cases and 3887 controls for CYP1B1 Asn453Ser polymorphism (from 5 studies), and 1301 cases and 2045 controls for CYP1B1 Ala119Ser polymorphism (from 4 studies). Seven studies included enough information in a subgroup analysis by smoking status.…”