Circulating markers of cellular immune activation in pre-diagnostic human serum in relation to lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Cell-mediated immunity may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), kynurenine metabolite—quinolinic acid (QA), and neopterin as markers of interferon-gamma-induced cellular immune activation with lung cancer risk in 5,364 cases and 5,364 individually matched control subjects from 20 prospective cohorts included the international Lung Cancer Cohort Consortium (LC3). Tryptophan, kynurenine, QA, and neopterin were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with different levels of these metabolites and KTR were calculated using conditional logistic regression with adjustment for matched smoking variables and circulating cotinine. Overall, the highest quintiles of circulating kynurenine, KTR, QA and neopterin were associated with a 20–30% higher risk of lung cancer, and tryptophan with a 15% lower risk compared with the lowest quintile (all P(trend)