Well-Done Meat Intake, Heterocyclic Amine Exposure, and Cancer Risk

Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA.
Nutrition and Cancer (Impact Factor: 2.32). 07/2009; 61(4):437-46. DOI: 10.1080/01635580802710741
Source: PubMed


High intake of meat, particularly red and processed meat, has been associated with an increased risk of a number of common cancers such as breast, colorectum, and prostate in many epidemiological studies. Heterocyclic amines (HCAs) are a group of mutagenic compounds found in cooked meats, particularly well-done meats. HCAs are some of most potent mutagens detected using the Ames/salmonella tests and have been clearly shown to induce tumors in experimental animal models. Over the past 10 years, an increasing number of epidemiological studies have evaluated the association of well-done meat intake and meat carcinogen exposure with cancer risk. The results from these epidemiologic studies were evaluated and summarized in this review. The majority of these studies have shown that high intake of well-done meat and high exposure to meat carcinogens, particularly HCAs, may increase the risk of human cancer.

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    • "The mechanisms are thought to involve the generation of Heterocyclic Amines (HCAs) and haem compounds catalysing oxidative damage. HCA’s are produced when creatinine reacts with amino acids and sugars at high temperatures [6]. The longer the meat is cooked and at higher temperatures results in a greater number of HCAs being generated [7]. "
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    ABSTRACT: Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. To review the key evidence available for potential chemopreventive nutrients. The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population.
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    • "A direct association between pancreatic cancer and meat, particularly red meat, has been reported in several epidemiological studies (Stolzenberg-Solomon et al, 2007; World Cancer Research Fund and American Institute for Cancer Research, 2007; Zheng and Lee, 2009; Polesel et al, 2010; Anderson et al, 2012; Larsson and Wolk, 2012). Thus, the limited intake of (red) meat is another characteristic of the Mediterranean diet, which favourably influences pancreatic cancer risk. "
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    ABSTRACT: Background: The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer. Methods: We analysed data from two case–control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, respectively. A Mediterranean Diet Score (MDS) summarising major characteristics of the Mediterranean diet was used in the two studies separately and overall. Two further scores of adherence to the Mediterranean diet were applied in the second study only, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI). Results: Odds ratios (ORs) for increasing levels of the scores (i.e., increasing adherence) were estimated using multiple logistic regression models. Odds ratio for a MDS score ⩾6 compared with <3 was 0.57 (95% confidence interval (CI) 0.34–0.95) in the first study, 0.51 (95% CI 0.29–0.92) in the second study, and 0.48 (95% CI 0.35–0.67) overall. A trend of decreasing risk was observed also for the MDP and MAI the ORs for the highest vs the lowest quintile being 0.44 (95% CI 0.27–0.73) for MDP and 0.68 (95% CI 0.42–1.11) for the MAI. The results were consistent across strata of age, sex, education, body mass index, alcohol drinking, tobacco smoking, and diabetes. Conclusion: Our study provides evidence that a priori-defined scores measuring adherence to the Mediterranean diet are favourably associated with pancreatic cancer risk.
    Full-text · Article · Aug 2013 · British Journal of Cancer
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    • "Based on current evidence the International Agency for Research on Cancer (IARC) classified 2-Amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) as a probable human carcinogen (class 2A) and eight other HAAs as possible human carcinogens (class 2B) (IARC, 1993). Human epidemiological studies indicate association of well-done meat intake with increased cancer risk (Zheng and Lee, 2009) however the evidence is insufficient to ascribe the increased risk specifically to HAAs. "
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    ABSTRACT: Heterocyclic aromatic amines (HAAs) are potential human carcinogens formed in well-done meats and fish. The most abundant are 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2- Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5- f]quinoxaline (4,8-DiMeIQx) and 2-Amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ). HAAs exert genotoxic activity after metabolic transformation by CYP1A enzymes, that is well characterized, however the genomic and intervening responses are not well explored. We have examined cellular and genomic responses of human hepatoma HepG2 cells after 24h exposure to HAAs. Comet assay revealed increase in formation of DNA strand breaks by PhIP, MeIQx and IQ but not 4,8-DiMeIQx, whereas increased formation of micronuclei was not observed. The four HAAs up-regulated expression of genes encoding metabolic enzymes CYP1A1, CYP1A2 and UGT1A1 and expression of TP53 and its downstream regulated genes CDKN1A, GADD45α and BAX. Consistent with the up-regulation of CDKN1A and GADD45α the cell-cycle analysis showed arrest in S-phase by PhIP and IQ, and in G1- phase by 4,8-DiMeIQx and MeIQx. The results indicate that upon exposure to HAAs the cells respond with the cell-cycle arrest, which enables cells to repair the damage or eliminate them by apoptosis. However, elevated expression of BCL2 and down-regulation of BAX may indicate that HAAs could suppress apoptosis meaning higher probability of damaged cells to survive and mutate.
    Full-text · Article · Jun 2013 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
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