Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer?

Abstract

High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied th effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite. Increased intake of red meat induced a significant (P<0.024) 3-fold increase from 40 + or - 7 to ab average of 113 + or - 25 microgram/day NOC, a range of exposure in faeces similar to that from tobacco-specific NOC in cigarette smoke. THe diets were isoenergetic and contained equal amounts of fat, but concentrations of heterocyclic amines were low. Faecal excretion of the promotor ammonia was significantly increased to 6.5 + or - 1.08 mmol/day. When the high red meat diets were supplemented with 20 g phytate-free wheat bran in six volunteers there was no reduction in NOC levels (mean 138 + or - 41 microgram/day NOC), but faecal weight increased. Higher starch and non-starch polysaccharide intakes reduced intraluminal cross-linking in microcapsules (r=-0.77) and reduced faecal pH (r=-0.64). In two volunteers there was no effect of 600 g white meat and fish o faecal NOC (mean low white meat diet 68 + or - 10 microgram/day, high white meat 56 + or -6 microgram/day nor on faecal nitrate, nitrite and iron. Faecal nitrite levels increased on changing from a white to red meat diet (mean high white meat diet 46 + or - 7 mg/day, high red meat diet mean 80 + or - 7 mg/day.) Increased endogenous production of NOC and precursors from increased red meat, but not white meat and fish, consumption may be relevant to the aetiology of colorectal cancer.

Iron and Cancer Risk—A Systematic Review and Meta-analysis of the Epidemiological Evidence

“…Bingham and colleagues conducted a human experiment where they exposed male volunteers to high amounts of red meat or heme iron. They found that these individuals produced higher levels of fecal N-nitroso compounds than when exposed to the same amounts of white meat or ferrous iron (48,49). (Fig.…”

Meat Processing and Colon Carcinogenesis: Cooked, Nitrite-Treated, and Oxidized High-Heme Cured Meat Promotes Mucin-Depleted Foci in Rats

“…Red meat enhances the formation of putative carcinogenic N-nitroso compounds in human feces (8)(9)(10). But N-nitroso compounds brought into the rat intestine by a bacon-based diet did not initiate nor promote preneoplastic lesions in rat colon (11).…”

Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

“…It has been suggested that N-nitroso compounds, present in processed meat or endogenously formed (Bingham et al, 1996), may induce G4A transitions at the second base of codon 12 or 13 of the K-ras gene in the human colon (Hughes et al, 2001). Hightemperature cooking of meat proteins generates heterocyclic aromatic amines (HAA), whereas the process of grilling and smoking of meat generates polycyclic aromatic hydrocarbons (PAH) as a result of fat dropping on open flames.…”