CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population

摘要

Aims: In this study, the effects of four single nudeotide polymorphisms (SNPs), -3860G>A, -2467delT, - 739T>G and - 163C>A, of CYP1A2 gene on lung cancer were evaluated in Tunisian population. Main methods: 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). The genotyping for the SNPs - 3860 G>A, -2467delT, -739T>Gand -163C> A was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis.Key findings: The results showed that smokers with CYP1A2 gene polymorphisms were associated with an increased risk for the development of lung AD. There was however no significant increased risk of developing lung SCC in smokers having CYP1A2 gene polymorphisms. An increased risk of developing AD was observed in smokers who are carriers of at least one copy of-3680A or - 739G giving a significant odds ratio (OR) of 6.02 (CI = 2.91-12.9) and 3.01 (CI=1.54-5.98), respectively.Significance: These genotyping data are consistent with the hypothesis that tobacco-specific-N-nitrosamines (TSN) such as 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) are major contributors to the development of lung AD and that CYP1A2 gene product plays an important role in the metabolic activation of NNK. This study suggests that SNPs of CYP1A2 could be considered as promising biomarkers in the aetiology of lung AD in smokers.