Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status

Am J Clin Nutr. 2017 Apr;105(4):897-904. doi: 10.3945/ajcn.116.139337. Epub 2017 Mar 8.

Abstract

Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5'-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings.Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk.Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine:XA (HK:XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status.Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK:XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK:XA and PAr, the findings were mainly observed in study participants with <10.5 y of follow-up between sampling and diagnosis.Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.

Keywords: biomarkers; colorectal cancer; inflammation; metabolite ratios; vitamin B-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / prevention & control
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / etiology
  • Kynurenine / analogs & derivatives*
  • Kynurenine / blood
  • Male
  • Middle Aged
  • Nutritional Status*
  • Odds Ratio
  • Oxidative Stress
  • Prospective Studies
  • Pyridoxal / blood
  • Pyridoxal Phosphate / blood
  • Pyridoxic Acid / blood
  • Sweden
  • Vitamin B 6 / blood*
  • Vitamin B 6 Deficiency / blood
  • Vitamin B 6 Deficiency / complications*
  • Xanthurenates / blood*

Substances

  • Biomarkers
  • Xanthurenates
  • 3-hydroxykynurenine
  • Kynurenine
  • Pyridoxal
  • xanthurenic acid
  • Pyridoxic Acid
  • Pyridoxal Phosphate
  • Vitamin B 6