CYP1A2, a highly inducible enzyme in the smoking population, may also represent a determinant of pharmacokinetic and pharmacological variability of icotinib, especially in lung cancer patients with smoking history.
In addition, as the gene polymorphisms reflected, the polymorphisms of CYP1A1 (-3801T/C and -4889A/G), CYP1A2 (- 163C/A and -2467T/delT), CYP1B1 (-48G/C, -119G/T and -432G/C), CYP2E1 (-1293G/C and -1053 C/T) have been associated with an increased risk of lung cancer.
Subgroup analysis indicated that there was an associationbetween CYP1A2 -163C>A polymorphism and lung cancer risk for population-based controls, a trend risk for SCCL (squamous cell carcinoma of lung) and Caucasians.
Several CYP1A2 haplotypes and diplotypes containing the -2467delT variant were associated with lower lung cancer risk; however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine.
These results suggest that the rs3569413 polymorphism of the CYP1A2 gene is associated with an increased risk of lung cancer and the rs762551 polymorphism of the CYP1A2 gene might be a potential biomarker for the risk of cancer among Caucasians.
We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health."
Four polymorphisms of CYP1A2 gene were analysed in 109 healthy smokers and in 101 lung cancer cases, including 63 with squamous cell carcinoma (SCC) and 41 with adenocarcinoma (AD).
CYP1A1 is a gene involved in the high aryl hydrocarbon hydroxylase -inducible phenotype, which is a genetically-determined variation among individuals that has been associated with lung cancer risk.
We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design.
We suggested that light smokers with intermediate-slow NAT2 activity were at highest risk for lung cancer and the gene-gene interaction based on intermediate-slow NAT2 activity and high CYP1A2 activity would be increased a lung cancer risk among never smokers.
The association of genetic polymorphisms of CYP1A2 and NAT2, two major enzymes responsible for the metabolism of heterocyclic amines, with lung cancer has been investigated with inconclusive results.
There was no effect of CYP1A2 activity on overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and cruciferous vegetable intake].
Three examples of pharmacogenetic risk factors are discussed: the first two are p450 enzymes whose activity has been associated with susceptibility to lung cancer (debrisoquine hydroxylase, aryl hydrocarbon hydroxylase), and the last, N-acetyltransferase, a non-p450 enzyme, has been associated with bladder cancer susceptibility.
Epidemiologic evidence for the association of aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of difficulties in the assay and subsequent confounding factors.
Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: a correlation with family histories of cancer.