Mollerup Steen, Berge Gisle, Baera Rita, Skaug Vidar, Hewer Alan, Phillips David H, Stangeland Lodve, Haugen Aage
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway.
Int J Cancer. 2006 Aug 15;119(4):741-4. doi: 10.1002/ijc.21891.
It is controversial whether women have a higher lung cancer susceptibility compared to men. We previously reported higher levels of smoking-related bulky DNA adducts in female lungs. In a pilot study (27 cases), we also found a higher level of female lung cytochrome P4501A1 (CYP1A1) gene expression. In the present extended study we report on the pulmonary expression of several genes involved in polycyclic aromatic hydrocarbon bioactivation in relation to sex, smoking and DNA adducts. CYP1A1, CYP1B1, aryl hydrocarbon receptor and microsomal epoxide hydrolase gene expression was measured by quantitative real-time reverse transcriptase-PCR in 121 normal lung tissue samples. The expression of CYP1A1 and CYP1B1 was significantly higher among current smokers compared to ex-smokers and never-smokers. Among current smokers, females had a 3.9-fold higher median level of CYP1A1 compared to males (p = 0.011). CYP1B1 expression was not related to sex. Lung DNA adducts (measured by 32P-postlabeling) were highly significantly related to CYP1A1 (p < 0.0001) irrespective of smoking-status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to lung cancer among females.
与男性相比，女性是否具有更高的肺癌易感性存在争议。我们之前报道过女性肺部中与吸烟相关的大分子DNA加合物水平较高。在一项试点研究（27例）中，我们还发现女性肺细胞色素P4501A1（CYP1A1）基因表达水平较高。在本项扩展研究中，我们报告了与性别、吸烟和DNA加合物相关的几种参与多环芳烃生物活化的基因的肺部表达情况。通过定量实时逆转录聚合酶链反应在121份正常肺组织样本中检测了CYP1A1、CYP1B1、芳烃受体和微粒体环氧化物水解酶基因的表达。与既往吸烟者和从不吸烟者相比，当前吸烟者中CYP1A1和CYP1B1的表达显著更高。在当前吸烟者中，女性CYP1A1的中位数水平比男性高3.9倍（p = 0.011）。CYP1B1的表达与性别无关。无论吸烟状态如何，肺DNA加合物（通过32P后标记法测量）与CYP1A1高度显著相关（p < 0.0001）。我们的结果与CYP1A1在肺DNA加合物形成中起重要作用的假设一致，并支持女性对肺癌具有更高易感性的观点。
