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.