TY - JOUR
T1 - Circulating tryptophan metabolites and risk of colon cancer
T2 - Results from case-control and prospective cohort studies
AU - Papadimitriou, Nikos
AU - Gunter, Marc J.
AU - Murphy, Neil
AU - Gicquiau, Audrey
AU - Achaintre, David
AU - Brezina, Stefanie
AU - Gumpenberger, Tanja
AU - Baierl, Andreas
AU - Ose, Jennifer
AU - Geijsen, Anne J. M. R.
AU - van Roekel, Eline H.
AU - Gsur, Andrea
AU - Gigic, Biljana
AU - Habermann, Nina
AU - Ulrich, Cornelia M.
AU - Kampman, Ellen
AU - Weijenberg, Matty P.
AU - Ueland, Per Magne
AU - Kaaks, Rudolf
AU - Katzke, Verena
AU - Krogh, Vittorio
AU - Bueno-de-Mesquita, Bas
AU - Ardanaz, Eva
AU - Travis, Ruth C.
AU - Schulze, Matthias B.
AU - Sánchez, Maria-José
AU - Colorado-Yohar, Sandra M.
AU - Weiderpass, Elisabete
AU - Scalbert, Augustin
AU - Keski-Rahkonen, Pekka
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
AB - Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
UR - http://www.scopus.com/inward/record.url?scp=85110045545&partnerID=8YFLogxK
U2 - 10.1002/ijc.33725
DO - 10.1002/ijc.33725
M3 - Article
SN - 0020-7136
VL - 149
SP - 1659
EP - 1669
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 9
ER -