Impaired functional vitamin B6 status is associated with increased risk of lung cancer

Research output: Contribution to journalArticle


Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5′-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case–control study consisting of 5,364 matched case–control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10–1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.


  • Despoina Theofylaktopoulou
  • Øivind Midttun
  • Per M. Ueland
  • Klaus Meyer
  • Anouar Fanidi
  • Wei Zheng
  • Xiao Ou Shu
  • Yong Bing Xiang
  • Ross Prentice
  • Mary Pettinger
  • Cynthia A. Thomson
  • Graham G. Giles
  • Allison Hodge
  • Qiuyin Cai
  • William J. Blot
  • Jie Wu
  • Mikael Johansson
  • Johan Hultdin
  • Kjell Grankvist
  • Victoria L. Stevens
  • Marjorie M. McCullough
  • Stephanie J. Weinstein
  • Demetrius Albanes
  • Regina Ziegler
  • Neal D. Freedman
  • Arnulf Langhammer
  • Kristian Hveem
  • Marit Næss
  • Howard D. Sesso
  • J. Michael Gaziano
  • Julie E. Buring
  • I. Min Lee
  • Gianluca Severi
  • Xuehong Zhang
  • Meir J. Stampfer
  • Jiali Han
  • Stephanie A. Smith-Warner
  • Anne Zeleniuch-Jacquotte
  • Loic Le Marchand
  • Jian Min Yuan
  • Renwei Wang
  • Lesley M. Butler
  • Woon Puay Koh
  • Yu Tang Gao
  • Nathaniel Rothman
  • Kala Visvanathan
  • Miranda R. Jones
  • Caroline Relton
  • Paul Brennan
  • Mattias Johansson
  • Arve Ulvik
External organisations
  • University of Bergen
  • Haukeland University Hospital
  • International Agency for Research on Cancer, World Health Organization
  • University of Cambridge
  • Vanderbilt University School of Medicine
  • Renji Hospital
  • Fred Hutchinson Cancer Research Center
  • University of Arizona
  • Cancer Council Victoria
  • University of Melbourne
  • Umeå University
  • American Cancer Society
  • National Cancer Institute, USA
  • Norwegian University of Science and Technology
  • Brigham and Women's Hospital / Harvard Medical School
  • Veterans Health Administration
  • Human Genetics Foundation (HuGeF)
  • University of Paris-Sud
  • New York University
  • University of Hawaii Cancer Center
  • University of Pittsburgh Cancer Institute
  • University of Pittsburgh
  • National University of Singapore
  • Shanghai Jiao Tong University
  • Johns Hopkins Bloomberg School of Public Health
  • University of Newcastle upon Tyne
  • University of Bristol
  • Bevital AS
  • Harvard T.H. Chan School of Public Health
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • 3-hydroxykynurenine:xanthurenic acid, functional vitamin B6 marker, Lung Cancer Cohort Consortium, pyridoxal 5′-phosphate
Original languageEnglish
Pages (from-to)2425-2434
Number of pages10
JournalInternational Journal of Cancer
Issue number12
Publication statusPublished - 2018 Jun 15
Publication categoryResearch