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

Theofylaktopoulou, Despoina; Midttun, Øivind; Ueland, Per M.; Meyer, Klaus; Fanidi, Anouar; Zheng, Wei; Shu, Xiao Ou; Xiang, Yong Bing; Prentice, Ross and Pettinger, Mary, et al. (2018) In International Journal of Cancer 142(12). p.2425-2434
Abstract

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... (More)

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.

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keywords
3-hydroxykynurenine:xanthurenic acid, functional vitamin B6 marker, Lung Cancer Cohort Consortium, pyridoxal 5′-phosphate
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International Journal of Cancer
volume
142
issue
12
pages
10 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85045757473
ISSN
0020-7136
DOI
10.1002/ijc.31215
language
English
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yes
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c6d1cb53-a8d7-4920-a9ff-f0064cfccf4c
date added to LUP
2018-05-02 14:16:46
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2019-08-14 04:15:38
@article{c6d1cb53-a8d7-4920-a9ff-f0064cfccf4c,
  abstract     = {<p>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 (OR<sub>4th</sub>         <sub>vs.</sub>         <sub>1st</sub>) 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.</p>},
  author       = {Theofylaktopoulou, Despoina and Midttun, Øivind and Ueland, Per M. and Meyer, Klaus and Fanidi, Anouar and Zheng, Wei and Shu, Xiao Ou and Xiang, Yong Bing and Prentice, Ross and Pettinger, Mary and Thomson, Cynthia A. and Giles, Graham G. and Hodge, Allison and Cai, Qiuyin and Blot, William J. and Wu, Jie and Johansson, Mikael and Hultdin, Johan and Grankvist, Kjell and Stevens, Victoria L. and McCullough, Marjorie M. and Weinstein, Stephanie J. and Albanes, Demetrius and Ziegler, Regina and Freedman, Neal D. and Langhammer, Arnulf and Hveem, Kristian and Næss, Marit and Sesso, Howard D. and Gaziano, J. Michael and Buring, Julie E. and Lee, I. Min and Severi, Gianluca and Zhang, Xuehong and Stampfer, Meir J. and Han, Jiali and Smith-Warner, Stephanie A. and Zeleniuch-Jacquotte, Anne and Le Marchand, Loic and Yuan, Jian Min and Wang, Renwei and Butler, Lesley M. and Koh, Woon Puay and Gao, Yu Tang and Rothman, Nathaniel and Ericson, Ulrika and Sonestedt, Emily and Visvanathan, Kala and Jones, Miranda R. and Relton, Caroline and Brennan, Paul and Johansson, Mattias and Ulvik, Arve},
  issn         = {0020-7136},
  keyword      = {3-hydroxykynurenine:xanthurenic acid,functional vitamin B6 marker,Lung Cancer Cohort Consortium,pyridoxal 5′-phosphate},
  language     = {eng},
  month        = {06},
  number       = {12},
  pages        = {2425--2434},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Impaired functional vitamin B6 status is associated with increased risk of lung cancer},
  url          = {http://dx.doi.org/10.1002/ijc.31215},
  volume       = {142},
  year         = {2018},
}