Carcinogenesis Advance Access published online on March 14, 2008
Carcinogenesis, doi:10.1093/carcin/bgm286
DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis
1 Life Sciences and Epidemiology Unit, ISI Foundation, Torino, Italy
2 University of Copenhagen, Dept. of Environmental and Occupational Health
3 Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO- Scientific Institute of Tuscany, Florence, Italy
4 Mailman School of Public Health, Columbia University, New York, US
5 Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton SM2 5NG, UK
6 Department of Environmental and Occupational Medicine, University of Aarhus, Aarhus, Denmark
7 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
8 Department of Epidemiology and Public Health, Imperial College London, Norfolk Place, W2 1PG London UK
10 Gerard Hoek, Michal Krzyzanowski, Luisa Airoldi, Alison Dunning, Seymour Garte, Pierre Hainaut, Christian Malaveille, Kim Overvad, 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
9 Correspondence to: Prof. Paolo Vineis, Dept. of Epidemiology and Public Health, Norfolk Place, Imperial College London, London W2 1PG UK, tel. 0044 20 75943372 fax 0044 2075943196 e-mail p.vineis{at}mperial.ac.uk
Background - Bulky DNA adducts are biomarkers of exposure to aromatic compounds, and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain.
Methods - We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51 to 137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies.
Results - In the pooled analysis a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% Confidence Interval, 1 to 28%; using the WMD (weighted mean difference) method, 0.15 standard deviation units higher adducts in cases then in controls). The association was evident only in current smokers, and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, while the results in never smokers were equivocal; in former smokers no association was detected.
Conclusion - The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years.
Key Words: DNA adducts • cancer • epidemiology
Received September 25, 2007; revised November 30, 2007; accepted December 1, 2007.