Raimondi Sara, Boffetta Paolo, Anttila Sisko, Bröckmoller Jürgen, Butkiewicz Dorota, Cascorbi Ingolf, Clapper Margie L, Dragani Tommaso A, Garte Seymour, Gsur Andre, Haidinger Gerald, Hirvonen Ari, Ingelman-Sundberg Magnus, Kalina Ivan, Lan Qing, Leoni Vera Piera, Le Marchand Loïc, London Stephanie J, Neri Monica, Povey Andrew C, Rannug Agneta, Reszka Edyta, Ryberg David, Risch Angela, Romkes Marjorie, Ruano-Ravina Alberto, Schoket Bernadette, Spinola Monica, Sugimura Haruhiko, Wu Xifeng, Taioli Emanuela
Fondazione Policlinico IRCCS, Molecular and Genetic Epidemiology Unit, via Pace 9, 20122-Milano, Italy.
Mutat Res. 2005 Dec 30;592(1-2):45-57. doi: 10.1016/j.mrfmmm.2005.06.002. Epub 2005 Jul 11.
Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors.
We evaluated the role of the metabolic gene polymorphisms CYP1A1MspI, CYP1A1Ile462Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed.
A significant association between lung cancer and CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR=2.04, 95% CI 1.17-3.54). GSTT1 deletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR=1.66, 95% CI 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers.
Our analysis confirms previous findings that CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers.
由于遗传因素可能在低剂量致癌物暴露导致肺癌发生过程中发挥重要作用，非吸烟者是研究遗传易感性及其与环境因素相互作用的良好模型。
我们在国际环境致癌物遗传易感性协作研究（GSEC）中评估了代谢基因多态性CYP1A1MspI、CYP1A1Ile462Val、GSTM1和GSTT1在非吸烟肺癌患者中的作用。从GSEC数据库中选取非吸烟者（定义为从未定期吸烟的受试者）。我们汇总了来自21项病例对照研究的原始数据，共涉及2764名白种人（555例病例和2209例对照）和383名亚洲人（113例病例和270例对照）。进行了异质性检验和纳入偏倚检验。
在白种人中观察到肺癌与CYP1A1Ile462Val多态性之间存在显著关联（校正比值比=2.04，95%可信区间1.17 - 3.54）。仅当分析限于纳入健康对照的研究时，GSTT1缺失似乎是白种人非吸烟者患肺癌的一个危险因素（校正比值比=1.66，95%可信区间1.12 - 2.46）。观察到CYP1A1野生型、GSTM1缺失型和GSTT1非缺失型基因型组合对肺癌有保护作用。在亚洲非吸烟者中，所分析的多态性均与肺癌无关。
我们的分析证实了先前的发现，即CYP1A1Ile462Val多态性可能在白种人非吸烟者的肺癌发生中起作用。
