Markers of vitamin B6 status and metabolism as predictors of incident cancer: The Hordaland Health Study

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'-phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3-hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4-pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community-based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998-99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site-specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow-up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate-adjusted Cox-regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI)=1.31 (1.12-1.52) per two standard deviation (SD) increment (p<0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI)=2.46 (1.49-4.05) per two SD increment (p<0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis. What's new? Vitamin B6 status is reflected in the measure of its active form, pyridoxal 5'-phosphate (PLP). Studies disagree, however, as to whether or not PLP measures are meaningful in relation to cancer risk, which has necessitated a search for additional markers of vitamin B6 status. In this study, inflammation-related changes in vitamin B6 catabolism were captured effectively by a novel marker, the 4-pyridoxic acid (PA) /(pyridoxal (PL)+PLP) ratio (PAr). Analyses based on the detection of PAr suggest that increased vitamin B6 metabolism and disposal are linked to increased cancer risk, particularly for lung cancer.