The association of dietary intake of heterocyclic aromatic amines and colorectal adenomas is modified by the intake of flavonols: Results from the EPIC-Heidelberg cohort

A15

Purpose of the study: Meat consumption has been shown to be associated with an increased risk of colorectal cancer in several epidemiological studies. Heterocyclic aromatic amines (HCA), which arise from cooking meat and fish at high temperatures, are thought to contribute to this increased risk. On the other hand, secondary plant compounds such as flavonols might counteract the negative effects of HCA. We examined the association of HCA intake and the risk of colorectal adenomas within the EPIC-Heidelberg cohort study. In addition, we examined wether this association is modified by the dietary intake of secondary plant products such as flavonols.
 >Material and Methods: Within the EPIC-Heidelberg cohort (n=25,540), detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was assessed using information on amount of meat consumption, cooking methods, and degree of browing. Intake of flavoidnoids was estimated using previously published data on secondary plant components in food. Until the end of the 3rd follow-up (June 2007), 516 verified colorectal adenomas were observed. Controls were participants with a negative colonoscopy (n=4482). Cox proportional hazards regression was used to examine the association between HCA intake and colorectal adenoma risk taking into account age, sex, body mass index, family history of colorectal cancer, physical activity, intake of non-steroidal anti-inflammatory drugs, smoking, education as well as intake of energy, alcohol, milk/milk products, and fibre. Stratified models were run for high and low intake of flavonols.
 >Results: A high intake of total HCA (relative risk (RR)=1.34, 95% confidence interval (CI) 1.02-1.75 4th vs 1st quartile) and of the most abundant HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (RR=1.46, 95% CI 1.11-1.91) were associated with colorectal adenoma risk in the multvariate analysis. These associations were stronger in participants with a low flavonoid intake (total HCA RR=1.47, 95% CI 0.97-2.18; p-trend=0.03; PhIP RR=1.76, 95% CI 1.17-2.65; p-trend=0.01) than in participants with high flavonol intake (total HCA RR=1.32, 95% CI 0.91-1.92, p-trend=0.11; PhIP RR=1.24, 95% CI 0.85-1.80,p-trend=0.14), although the p-values for interaction were not statistically significant (total HCA p-interaction=0.18, p-interaction=PhIP 0.16). No statistically significant associations were observed between the intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-3,4,8-trimethylimidazo[4,5-f ]quinoxaline (DiMeIQx) and the risk for colorectal adenomas.
 >Conclusions: The observation of a higher risk of colorectal adenomas in participants with low flavonol intake than in those with a high intake comfirms the hypothesis that a higher intake of secondary plant products might partially protect from adverse effects of HCA. Protective effects might be due to their effects on phase-1 and phase-2 metabolism.