Red meat and endogenous N-nitrosation as risk factors for colorectal cancer

• Main Author: Cross, A. J.
• Published: University of Cambridge 2002
• Subjects: 616.07
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598185

This Thesis investigated the role of red meat consumption on endogenous <i>N</i>-nitrosation. Results from previous work in conjunction with the results obtained from this study clearly demonstrate a dose-response effect of red meat on the level of faecal apparent total <i>N-</i>nitroso compounds (ATNC). This may be important because red meat is a proposed risk factor for colorectal cancer and many <i>N</i>-nitroso compounds (NOCs) are known carcinogens. Red meat may increase the endogenous formation of NOCs by increasing the amount of nitrosatable substrates arriving in the large intestine. This was examined by comparing the effect of white meat and a high protein vegetarian diet with the effects of a high red meat diet. The high red meat diet induced approximately a four-fold increase in faecal ATNC levels in two separate studies (p = <0.025), whereas neither a high white meat diet nor a high protein vegetarian diet significantly affected endogenous <i>N</i>-nitrosation. However, a haem supplement induced approximately a two-fold increase in faecal ATNC levels (p = <0.006), whereas an inorganic iron supplement did not significantly affect faecal ATNC. The majority of the faecal water samples from the intervention studies proved to be genotoxic by the Comet assay, although the degree of genotoxicity was not affected by diet. In addition, individuals who had undergone flexible sigmoidoscopy to detect the presence of adenomatous polyps were studied. Faecal specimens were collected and levels of ATNC measured from colorectal adenoma cases and polyp-free controls living at home. Increased faecal ATNC levels were associated with a significant increased sex-adjusted risk of colorectal adenoma (O.R. 2.2(1.0-4.6)). This risk was elevated when the individuals classified as high-risk for future development of colorectal cancer and controls were compared (O.R. 3.7 (1.2-11.3)). Dietary analysis showed that red meat intake was associated with risk of adenoma when the high-risk individuals were compared with controls (O. R. 3.1 (1.0-9.3)). However, risks were weakened and became non-significant after adjustment for smoking status.