Aromatic DNA adducts and risk of gastrointestinal cancers: a case-cohort study within the EPIC-Spain.

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 = 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 = 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.