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

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. StevensMarjorie 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, Ulrika Ericson, Emily Sonestedt, Kala Visvanathan, Miranda R. Jones, Caroline Relton, Paul Brennan, Mattias Johansson, Arve Ulvik

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2425-2434
Number of pages10
JournalInternational Journal of Cancer
Issue number12
StatePublished - Jun 15 2018


  • 3-hydroxykynurenine:xanthurenic acid
  • Lung Cancer Cohort Consortium
  • functional vitamin B6 marker
  • pyridoxal 5′-phosphate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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