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

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 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 (OR4thvs.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.

• Authors: 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 Naess, 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
• Journal: International journal of cancer (Int J Cancer) Vol. 142 Issue 12 Pg. 2425-2434 (06 15 2018) ISSN: 1097-0215 [Electronic] United States
• PMID: 29238985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 UICC.

Chemical References

• Biomarkers
• Vitamin B 6

Topics

• Aged
• Biomarkers (blood)
• Carcinoma, Squamous Cell (blood, pathology)
• Case-Control Studies
• Cohort Studies
• Female
• Humans
• Lung Neoplasms (blood, pathology)
• Male
• Middle Aged
• Odds Ratio
• Risk Factors
• Vitamin B 6 (blood)