649P - Diet-derived metabolites and the risk of colorectal cancer: A nested case-control study in a population-based cohort, the Singapore Chinese health study

Abstract

BackgroundDiet 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. MethodsWe 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). ResultsCompared 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<0.05). Valine was inversely associated with colon cancer (OR3rd vs 1st tertile 0.45; 95% CI, 0.25-0.81). 7 metabolites (glucose, mannose, propionic acid, DCA, GDCA, TDCA and glycolate) were associated with an increased risk of rectal cancer (all p<0.05). Only glucose significantly improved the risk prediction of rectal cancer. No metabolites led to an improvement in the predictive model for colon cancer. ConclusionsDysregulation 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 studyThe authors. FundingNational Medical Research Council. DisclosureAll authors have declared no conflicts of interest.