Aromatic DNA adducts and risk of gastrointestinal cancers. A case-cohort study within the EPIC-Spain
Couplée à la branche espagnole de la cohorte EPIC, cette étude (202 cas et 296 témoins) évalue l'association entre des composés aromatiques présents notamment dans les viandes transformées et la fumée de tabac, et le risque de cancers de l'estomac et du colon-rectum
Background: Colorectal and gastric cancer are associated with meat intake and tobacco smoke, maybe due to aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts. Methods:48 subjects diagnosed of gastric cancer and 154 of colorectal cancer during a 7-year follow-up period in the EPIC-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 32P-postlabelling 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 log2-transformed adduct concentration, we observed a RR=1.57 (CI 1.25-1.97) for colorectal cancer, which means a 57% increased risk associated with doubling the level of adducts, and 47% (RR=1.47, CI 1.07-2.00) increase in risk of gastric cancer. The association was more marked for colon than for rectal tumors, tough it remained significant in both localizations. Conclusions:The level of aromatic adducts in the DNA is independently associated with an increased risk of gastric and colorectal cancers. 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.