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. 2018 Jun 15;142(12):2425-2434.
doi: 10.1002/ijc.31215. Epub 2018 Jan 4.

Impaired Functional Vitamin B6 Status Is Associated With Increased Risk of Lung Cancer

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Free PMC article

Impaired Functional Vitamin B6 Status Is Associated With Increased Risk of Lung Cancer

Despoina Theofylaktopoulou et al. Int J Cancer. .
Free PMC article

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.

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

Conflict of interest statement

Competing interests

LMB is an employee of Genetech Inc. as of September 16.

Figures

Figure 1
Figure 1
Panel A. Distribution of smoking status stratified by sex in the different regions.Panel B. Distribution of smoking status and sex in the different cohorts.ATBC, The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study; CLUE, The Campaign Against Cancer and Stroke (CLUE I) and the Campaign Against Cancer and Heart Disease (CLUE II); CPS-II, The American Cancer Society Cancer Prevention Study-II Nutrition Cohort; HPFS, Health Professionals Follow-up Study; HUNT, The Nord-Trøndelag Health Study; MCCS, The Melbourne Collaborative Cohort Study; MDCS, The Malmö Diet and Cancer Study; MEC, The Multiethnic Cohort; NHS, The Nurses’ Health Study; NSHDS, The Northern Sweden Health and Disease Study Cohort; NYUWHS, The New York University Women’s Health Study; PHS, Physicians’ Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; SCCS, The Southern Community Cohort Study; SCHS, The Singapore Chinese Health Study; SCS, The Shanghai Cohort Study; SMHS, The Shanghai Men’s Health Study; SWHS, The Shanghai Women’s Health Study; WHI, The Women’s Health Initiative; WHS, Women’s Health Study.
Figure 2
Figure 2
Forestplot showing odds ratios for lung cancer comparing the fourth to the first quartile of HK:XAConditional logistic regression was performed for each cohort and was adjusted for smoking intensity using quartiles of cotinine among current smokers. Cases and controls were matched on age, sex, and smoking status. Results were combined using random effect models for each region and in all studies combined. HK:XA, 3-hydroxykynurenine:xanthurenic acid.
Figure 3
Figure 3
Forestplot showing odds ratios for lung cancer comparing the fourth to the first quartile of HK:XA in the different regions, stratified by gender. Conditional logistic regression was performed for each region and was adjusted for smoking intensity using quartiles of cotinine among current smokers. Cases and controls were matched on age, sex, and smoking status. Results were combined using random effect models. HK:XA, 3-hydroxykynurenine:xanthurenic acid.
Figure 4
Figure 4
Forestplot showing odds ratios for lung cancer comparing the fourth to the first quartile of HK:XA in the different regions, stratified by smoking status. Conditional logistic regression was performed for each subgroup and among current smokers (adjusted for smoking intensity using quartiles of cotinine among current smokers). Cases and controls were matched for age, sex, and smoking status. Results were combined using random effect models. HK:XA, 3-hydroxykynurenine:xanthurenic acid.

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