Research Article Aromatic DNA Adducts and Risk of Gastrointestinal Cancers: A Case–Cohort Study within the EPIC–Spain Antonio Agudo 1 , Marco Peluso 9 , Armelle Munnia 9 , Leila Luj an-Barroso 1 , María-Jos eS anchez 3,4 , Esther Molina-Montes 3,4 , Emilio S anchez-Cantalejo 3,4 , Carmen Navarro 3,5 , María-Jos e Tormo 3,5 , María-Dolores Chirlaque 3,5 , Aurelio Barricarte 3,6 , Eva Ardanaz 3,6 , Pilar Amiano 3,7 , Miren Dorronsoro 3,7 , J. Ram on Quir  os 8 , Sara Piro 9 , Catalina Bonet 1 ,N uria Sala 1,2 , and Carlos A. Gonz alez 1 Abstract Background: Colorectal (CRC) and gastric cancer (GC) are associated with meat intake and tobacco smoke, maybe because of aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts. Methods: Forty-eight subjects diagnosed of GC and 154 of CRC during a 7-year follow-up period in the European Prospective Investigation into Cancer and Nutrition–Spain cohort were compared with a sample of 296 subjects using a case–cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32 P-postlabeling technique. The relative risk (RR) and 95% confidence interval (CI), adjusted by relevant confounders were estimated by a modified version of Cox regression. Results: Using the log 2 -transformed adduct concentration, we observed a RR ¼ 1.57 (CI: 1.25–1.97) for CRC, which means a 57% increased risk associated with doubling the level of adducts, and 47% (RR ¼ 1.47, CI: 1.07–2.00) increase in risk of GC. The association was more marked for colon than for rectal tumors. Conclusions: The level of aromatic adducts in the DNA is independently associated with an increased risk of gastric and CRCs. This effect could be due to aromatic compounds present in tobacco smoke or formed in meat, but they could be also due to genotoxic compounds from other sources. Impact: Sources of aromatic compounds should be taken into account, in addition to known risk factors, in the research and prevention of tumors of the stomach, colon, and rectum. Cancer Epidemiol Biomarkers Prev; 21(4); 685–92. Ó2012 AACR. Introduction Colorectal cancer (CRC) is the third most common cancer in men and the second in women. Worldwide, 1.2 million new CRC cases and 609,000 deaths were expected to occur in 2008 (1). Gastric cancer (GC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer death worldwide, with an esti- mated 990,000 new cases and 738,000 cancer deaths the same year (1). Both tumors are multifactorial diseases and may result from a combination of genetic susceptibility and environ- mental exposures, including tobacco smoke and dietary factors. The International Agency for Research on Cancer has included the stomach, colon, and rectum among the tumor sites causally associated with tobacco smoking (2, 3). With regard to dietary factors, although the asso- ciation between meat and CRC is well established, the evidence for GC is less conclusive. A recent meta-analysis of prospective studies has shown that red and processed meat intake was associated with an increased risk of CRC, with similar results for colon and rectal cancer risk (4). Another meta-analysis reported that increased con- sumption of processed meat was associated with an increased risk of GC, though the possibility that this association was confounded or modified by other factors could not be ruled out (5). The risk of GC associated with meat consumption was also investigated in 2 large cohort study; one of them (6) found that red and processed meat intakes were associated with an increased risk of gastric Authors' Affiliations: 1 Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, 2 Molecular Epidemiology Group, Trans- lational Research Laboratory, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat; 3 CIBER de Epidemiología y Salud P ublica (CIBERESP), Barcelona; 4 Andalusian School of Public Health, Granada; 5 Department of Epidemiology, Murcia Health Council, Murcia; 6 Public Health Institute of Navarra, Pamplona; 7 Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the regional Government of the Basque Country, San Sebastian; 8 Public Health Direc- torate, Asturias, Spain; and 9 ISPO-Cancer Prevention and Research Insti- tute, Florence, Italy Corresponding Author: Antonio Agudo, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Av. Gran Via 199-203. L'Hospitalet de Llobregat, 08908 Spain. Phone: 34-93-260-7401 (ext. 3075); Fax: 34-93-260-7787; E-mail: a.agudo@iconcologia.net doi: 10.1158/1055-9965.EPI-11-1205 Ó2012 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention www.aacrjournals.org 685 Downloaded from http://aacrjournals.org/cebp/article-pdf/21/4/685/2275215/685.pdf by guest on 30 June 2022