Processed Meat and Colorectal Cancer: A Review of Epidemiologic and Experimental Evidence

Processed meat intake may be involved in the etiology of colorectal cancer, a major cause of death in affluent countries. The epidemiologic studies published to date conclude that the excess risk in the highest category of processed meat-eaters is comprised between 20 and 50% compared with non-eaters. In addition, the excess risk per gram of intake is clearly higher than that of fresh red meat. Several hypotheses, which are mainly based on studies carried out on red meat, may explain why processed meat intake is linked to cancer risk. Those that have been tested experimentally are (i) that high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acids; (ii) that cooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons; (iii) that carcinogenic N-nitroso compounds are formed in meat and endogenously; (iv) that heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products. Solving this puzzle is a challenge that would permit to reduce cancer load by changing the processes rather than by banning processed meat

Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium

Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary calcium, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60% beef meat were supplemented with calcium phosphate (33 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0•05% each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (þ30 %) and MDF (þ100 %) (P,0•001), which confirms our previous findings. Promotion was associated with increased faecal water TBARs ( £ 4) and cytotoxicity ( £ 2), and urinary DHN-MA excretion ( £ 15). Calcium fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-calcium control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that calcium can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient

Meat processing and colon carcinogenesis: Cooked, nitrite-treated and oxidized high-heme cured meat promotes mucin depleted foci in rats

Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 × 2 × 2 × 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P < 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar non nitrite-treated meat (P = 0.03) and with similar non oxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make non promoting processed meat

Freeze-Dried Ham Promotes Azoxymethane-Induced Mucin-Depleted Foci and Aberrant Crypt Foci in Rat Colon

Processed and red meat consumption is associated with the risk of colorectal cancer. Meta-analyses have suggested that the risk associated with processed meat is higher. Most processed meats are cured and cooked, which leads to formation of free nitrosyl heme. We speculated that free nitrosyl heme is more toxic than native myoglobin. The promoting effect of a freeze-dried, cooked, cured ham diet was looked for in a 100-day study. Colon carcinogenesis endpoints were aberrant crypt foci and mucin depleted foci (MDF). A second study (14 days) was designed 1) to compare the effect of ham, hemoglobin, and hemin; and 2) to test the effect of sodium chloride, nitrite, and phosphate in diet on early biomarkers associated with heme-induced promotion. In the 100-day study, control and ham-fed rats had 3.5 and 8.5 MDF/colon, respectively (P < 0.0001). Promotion was associated with cytotoxicity and lipid peroxidation. In the short-term study, cytotoxicity and lipid peroxidation of fecal water, and the urinary marker of lipid peroxidation, increased dramatically in ham- and hemin-fed rat. In contrast, the hemoglobin diet, sodium chloride, nitrite, phosphate diet had no effect. Freeze-dried cooked ham can promote colon carcinogenesis in a rodent model. Hemin, but not hemoglobin, mimicked ham effect on early biochemical markers associated with carcinogenesis

Consommation de viande et risque de cancer : Bilan critique des études épidémiologiques et expérimentales

L'effet de la consommation de viande sur le risque de cancer est un sujet controversé. Les méta-analyses de Norat et al. (2002) et Larsson et al. (2006) regroupent les résultats de toutes les études épidémiologiques. Elles montrent que la consommation de viande rouge est associée de façon significative avec une augmentation modérée du risque de cancer colorectal : l'excès de risque de cancer est de +19-22% pour la catégorie des gros mangeurs de viande rouge fraîche (bœuf, mouton, porc). Les charcuteries sont plus fortement associées au risque que la viande (+20-31%), surtout quand on rapporte le risque au poids de produit carné consommé par jour. Volailles et poissons ne sont pas des facteurs de risque. On manque de données pour conclure pour d'autres cancers majeurs (sein, prostate). Les recommandations actuelles sont donc de modérer la consommation de viande rouge et de charcuteries. Par ailleurs, nos études expérimentales suggèrent que le fer héminique est l'agent majeur de l'effet promoteur des viandes rouges, et que l’effet de l’hème peut être bloqué par le calcium des aliments

Calcium and α-Tocopherol Suppress Cured Meat Promotion of Chemically-Induced Colon Carcinogenesis in Rats and Reduce Associated Biomarkers in Human Volunteers

Background: Processed meat intake is associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: To investigate whether cured meat modulates biomarkers of cancer risk in human volunteers, and whether specific agents can suppress cured meat induced preneoplastic lesions in rats, and associated biomarkers in rats and in humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol and trisodium pyrophosphate) were added to cured meat given to groups of rats for fourteen days, then fecal biomarkers were measured. Based on these results, calcium and tocopherol were kept for further experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d), and to human volunteers in a cross-over study (180 g/d for 4 d). Rat colons were scored for mucin depleted foci, putative pre-cancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in rats and volunteers’ urine and feces. Results: Cured meat increased nitroso-compounds and lipoperoxidation in humans stools (both P<0.05). Calcium normalized both biomarkers in rats and humans’ feces, while tocopherol only decreased nitro-compounds in rats and lipoperoxidation in volunteers’ feces (all p<0.05). Lastly, calcium and tocopherol reduced the number of mucin depleted foci per colon in rats compared with non supplemented cured meat (P=0.01). Conclusion: The data suggest that addition of calcium carbonate to the diet or of α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured meat intake