A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer

Background Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B-6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B-6 status and risk of pancreatic cancer is lacking. Methods A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. Results Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxyky-nurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35-0.98) for the HAA: HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine: tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. Conclusions The inverse association between HAA or the HAA: HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.