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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.

SUBMITTER: Theofylaktopoulou D

PROVIDER: S-EPMC5908731 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Theofylaktopoulou Despoina D Midttun Øivind Ø Ueland Per M PM Meyer Klaus K Fanidi Anouar A Zheng Wei W Shu Xiao-Ou XO Xiang Yong-Bing YB Prentice Ross R Pettinger Mary M Thomson Cynthia A CA Giles Graham G GG Hodge Allison A Cai Qiuyin Q Blot William J WJ Wu Jie J Johansson Mikael M Hultdin Johan J Grankvist Kjell K Stevens Victoria L VL McCullough Marjorie M MM Weinstein Stephanie J SJ Albanes Demetrius D Ziegler Regina R Freedman Neal D ND Langhammer Arnulf A Hveem Kristian K Naess Marit M Sesso Howard D HD Gaziano J Michael JM Buring Julie E JE Lee I-Min IM Severi Gianluca G Zhang Xuehong X Stampfer Meir J MJ Han Jiali J Smith-Warner Stephanie A SA Zeleniuch-Jacquotte Anne A Le Marchand Loic L Yuan Jian-Min JM Wang Renwei R Butler Lesley M LM Koh Woon-Puay WP Gao Yu-Tang YT Rothman Nathaniel N Ericson Ulrika U Sonestedt Emily E Visvanathan Kala K Jones Miranda R MR Relton Caroline C Brennan Paul P Johansson Mattias M Ulvik Arve A

International journal of cancer 20180104 12

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:X ...[more]

PMID: 29238985

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Project description:Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.

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

Publications

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

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