Browsing ECNIS - Environmental Cancer Risk, Nutrition and Individual Susceptibility by Subject (MeSH)
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Heterocyclic aromatic amine intake increases colorectal adenoma risk: findings from a prospective European cohort study.BACKGROUND: Heterocyclic aromatic amines (HCAs), which arise from cooking meat and fish at high temperatures, may increase the risk of colorectal adenomas. Conversely, flavonoids might counteract the negative effects of HCAs. OBJECTIVE: The association between dietary HCA intake and colorectal adenoma incidence was investigated in a prospective cohort study. DESIGN: At recruitment (1994-1998), detailed information on diet, anthropometric measures, lifestyle, and medication use was assessed in 25,540 participants of the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort study. Dietary HCA intake was estimated by using information from food-frequency questionnaires on meat consumption, applied cooking methods, and preferred degree of browning. Until June 2007, 516 verified incident colorectal adenomas were identified. Participants with negative colonoscopy (n = 3966) were also included in the analytic cohort. Multivariate Cox proportional hazards regression was used to examine the association between colorectal adenoma risk and intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx). RESULTS: In multivariate analyses, the intake of PhIP as the most abundant dietary HCA was associated with an increased risk of colorectal adenoma (relative risk: 1.47; 95% CI: 1.13, 1.93; quartile 4 compared with quartile 1; P for trend = 0.002), but no statistically significant associations were observed for MeIQx and DiMeIQx intakes. In addition, adenoma risk also increased with the consumption of strongly or extremely browned meat (P for trend = 0.04). The association of PhIP intake with adenoma risk was most pronounced for small adenomas (P for trend = 0.01) and adenomas localized in the distal colon (P for trend = 0.002). CONCLUSION: The results of this first European cohort study support data from case-control studies of a positive association between HCA intake and colorectal adenoma risk.
The relationship between 8-oxo-7,8-dihydro-2'-deoxyguanosine level and extent of cytosine methylation in leukocytes DNA of healthy subjects and in patients with colon adenomas and carcinomas.It has been known for a long time that DNA hypomethylation occurs in many human cancers and precancerous conditions. However, the mechanisms of hypomethylation are largely unknown. It is possible that endogenous 8-oxo-7,8-dihydroguanine (8-oxoGua) level may be linked to aberrant DNA methylation of adjacent cytosine and in this way influences carcinogenesis. Therefore, the aim of the present study was to assess a possible link between 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) background level and 5-methylcytosine content in DNA from human leukocytes of healthy subjects (n=105) as well as in patients with colon adenomas (n=39) and carcinomas (n=50). Our results demonstrated statistically significant negative correlation between background level of 8-oxodG and 5-methylcytosine content in DNA isolated from leukocytes of healthy donors (r=-0.3436, p=0.0003). The mean content of 5-methylcytosine was significantly lower, while 8-oxodG level was significantly higher in leukocytes DNA of patients with colon adenomas and carcinomas in comparison with healthy subjects. The mean values for 5-methylcytosine were: 3.59+/-0.173% (healthy subjects), 3.38+/-0.128% (patients with adenomas), 3.40+/-0.208% (colon cancer patients). The mean values of 8-oxodG in DNA were, respectively: 4.67+/-1.276, 5.72+/-1.787, 5.76+/-1.884 8-oxodG per 10(6) dG molecules. DNA from affected tissue (colon) suffered from significant, about 10% reduction in cytosine methylation in comparison with leukocytes of the paired subjects. Our work provides the first in vivo evidence suggesting that increased levels of 8-oxodG in DNA may lead to carcinogenesis not only via mispair/mutagenic potential of the modified base but also through its ability to influence gene expression by affecting DNA methylation.