Peluso Marco, Munnia Armelle, Hoek Gerard, Krzyzanowski Michal, Veglia Fabrizio, Airoldi Luisa, Autrup Herman, Dunning Alison, Garte Seymour, Hainaut Pierre, Malaveille Christian, Gormally Emmanuelle, Matullo Giuseppe, Overvad Kim, Raaschou-Nielsen Ole, Clavel-Chapelon Francoise, Linseisen Jacob, Boeing Heiner, Trichopoulou Antonia, Trichopoulos Dimitrios, Kaladidi Anna, Palli Domenico, Krogh Vittorio, Tumino Rosario, Panico Salvatore, Bueno-De-Mesquita H Bas, Peeters Petra H, Kumle Merethe, Gonzalez Carlos A, Martinez Carmen, Dorronsoro Miren, Barricarte Aurelio, Navarro Carmen, Quiros J Ramón, Berglund Goran, Janzon Lars, Jarvholm Bengt, Day Nicholas E, Key Tim J, Saracci Rodolfo, Kaaks Rudolf, Riboli Elio, Vineis Paolo
Cancer Risk Factor Branch, CSPO-Scientific Institute of Tuscany Region, Florence, Italy.
Cancer Res. 2005 Sep 1;65(17):8042-8. doi: 10.1158/0008-5472.CAN-04-3488.
Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O3) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O3 indicates a possible role for photochemical smog in determining DNA damage.
目标是前瞻性地研究DNA加合物预测癌症的能力，并研究加合物的决定因素，特别是空气污染物。在欧洲癌症与营养前瞻性调查（EPIC）中开展的一项病例对照研究中对DNA加合物进行了测量。病例包括新诊断的肺癌（n = 115）、上呼吸道癌症（咽和喉；n = 82）、膀胱癌（n = 124）、白血病（n = 166）以及慢性阻塞性肺疾病或肺气肿死亡病例（n = 77），这些病例是在EPIC研究中的既往吸烟者和从不吸烟者经过7年中位随访后积累的。每个病例匹配3名对照用于问卷分析，每个病例匹配2名对照用于实验室分析。匹配标准为性别、年龄、吸烟状况、招募国家和随访时间。利用常规空气质量监测网络中监测站的浓度数据评估个体空气污染暴露情况。采用32P后标记技术对白细胞DNA加合物进行盲法分析。将可检测到的加合物与未检测到的加合物进行比较时，加合物与随后的肺癌风险相关，比值比（OR）为1.86 [95%置信区间（95%CI），0.88 - 3.93]。在从不吸烟者（OR，4.04；95%CI，1.06 - 15.42）和较年轻年龄组中，与肺癌的关联更强。在排除随访前36个月内发生的癌症后，OR为4.16（95%CI，1.24 - 13.88）。发现DNA加合物与臭氧（O3）浓度之间存在正相关。我们的前瞻性研究表明，白细胞DNA加合物可能预测从不吸烟者的肺癌风险。此外，DNA加合物水平与O3的关联表明光化学烟雾在决定DNA损伤方面可能发挥作用。
