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

机译：突尼斯人群中CYP1A2基因多态性与腺癌肺癌的风险

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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.
机译：目的：在这项研究中，评估了突尼斯人人群中CYP1A2基因的四个单核苷酸多态性（SNPs）-3860G> A，-2467delT，-739T> G和-163C> A对肺癌的影响。主要方法：在109名健康吸烟者和101例肺癌病例中分析了CYP1A2基因的4个多态性，包括63例鳞状细胞癌（SCC）和41例腺癌（AD）。通过聚合酶链反应（PCR）-限制性片段长度多态性分析对SNPs-3860 G> A，-2467delT，-739T> Gand -163C> A进行基因分型。与肺AD发展的风险增加有关。但是，具有CYP1A2基因多态性的吸烟者发生肺SCC的风险没有显着增加。在携带至少一份3680A或-739G拷贝的吸烟者中观察到罹患AD的风险增加，OR分别为6.02（CI = 2.91-12.9）和3.01（CI = 1.54-5.98）。意义：这些基因分型数据与以下假设相符：烟草特有的N-亚硝胺（TSN），例如4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是造成这种情况的主要因素肺AD的发展和CYP1A2基因产物在NNK的代谢活化中起重要作用。这项研究表明CYP1A2的SNPs可以被认为是吸烟者肺AD病因的有前途的生物标志物。

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