LAUSR

Abstract Background Diet is an important risk factor of colorectal cancer (CRC) and affects cancer risk through its effects on colonic microbial metabolism. Few population-based studies have examined the relationship between diet-derived metabolites and the risk of CRC in the context of Asian diet, microbiota composition and anatomical subsite. Methods We conducted a nested case-control study of 350 incident CRC (211 colon and 139 rectal) cases and 350 matched controls within the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women. Liquid and gas chromatography-mass spectrometries were used to quantify 61 plasma metabolites, including amino acids, carnitine, acylcarnitines, short chain fatty acids, bile acids, monosaccharides and organic compounds. Conditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). Results Compared to controls, colon cancer cases had statistically significant higher mean levels of glutamine, arginine, tauroursodeoxycholic acid (TUDCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), and lower mean levels of leucine and valine. Rectal cancer cases had statistically significant higher mean levels of mannose, glucose and isobutyric acid than controls. 9 metabolites [arginine, glutamine, mannose, deoxycholic acid (DCA), GDCA, taurochenodeoxycholic acid (TCDCA), TDCA, TUDCA and betaine] were associated with an increased risk of colon cancer (all p  Conclusions Dysregulation of secondary bile acids, monosaccharides, amino acids and short chain fatty acids may play a role in CRC development. Further studies are required to validate our findings. Legal entity responsible for the study The authors. Funding National Medical Research Council. Disclosure All authors have declared no conflicts of interest.