DNA adducts and lung cancer risk: a prospective study.

Abstract

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.

• Authors: Marco Peluso, Armelle Munnia, Gerard Hoek, Michal Krzyzanowski, Fabrizio Veglia, Luisa Airoldi, Herman Autrup, Alison Dunning, Seymour Garte, Pierre Hainaut, Christian Malaveille, Emmanuelle Gormally, Giuseppe Matullo, Kim Overvad, Ole Raaschou-Nielsen, Francoise Clavel-Chapelon, Jacob Linseisen, Heiner Boeing, Antonia Trichopoulou, Dimitrios Trichopoulos, Anna Kaladidi, Domenico Palli, Vittorio Krogh, Rosario Tumino, Salvatore Panico, H Bas Bueno-De-Mesquita, Petra H Peeters, Merethe Kumle, Carlos A Gonzalez, Carmen Martinez, Miren Dorronsoro, Aurelio Barricarte, Carmen Navarro, J Ramón Quiros, Goran Berglund, Lars Janzon, Bengt Jarvholm, Nicholas E Day, Tim J Key, Rodolfo Saracci, Rudolf Kaaks, Elio Riboli, Paolo Vineis
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 17 Pg. 8042-8 (Sep 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 16140979 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Adducts

Topics

• Adult
• Aged
• Case-Control Studies
• DNA Adducts (blood)
• Female
• Humans
• Lung Neoplasms (blood, genetics)
• Male
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Risk Factors