Abstract 1972
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 < 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.
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract