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 journalArticle

4 Citations (Scopus)

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 (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
Volume142
Issue number12
DOIs
StatePublished - Jun 15 2018
Externally publishedYes

Fingerprint

Vitamin B 6
Lung Neoplasms
Squamous Cell Carcinoma
Odds Ratio
Pyridoxal Phosphate
Biomarkers
Logistic Models
Smoking
Confidence Intervals
Inflammation
xanthurenic acid
3-hydroxykynurenine

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Theofylaktopoulou, D., Midttun, Ø., Ueland, P. M., Meyer, K., Fanidi, A., Zheng, W., ... Ulvik, A. (2018). Impaired functional vitamin B6 status is associated with increased risk of lung cancer. International Journal of Cancer, 142(12), 2425-2434. https://doi.org/10.1002/ijc.31215

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; Pettinger, Mary; Thomson, Cynthia A.; Giles, Graham G.; Hodge, Allison; Cai, Qiuyin; Blot, William J.; Wu, Jie; Johansson, Mikael; Hultdin, Johan; Grankvist, Kjell; Stevens, Victoria L.; McCullough, Marjorie M.; Weinstein, Stephanie J.; Albanes, Demetrius; Ziegler, Regina; Freedman, Neal D.; Langhammer, Arnulf; Hveem, Kristian; Næss, Marit; Sesso, Howard D.; Gaziano, J. Michael; Buring, Julie E.; Lee, I. Min; Severi, Gianluca; Zhang, Xuehong; Stampfer, Meir J.; Han, Jiali; Smith-Warner, Stephanie A.; Zeleniuch-Jacquotte, Anne; Le Marchand, Loic; Yuan, Jian Min; Wang, Renwei; Butler, Lesley M.; Koh, Woon Puay; Gao, Yu Tang; Rothman, Nathaniel; Ericson, Ulrika; Sonestedt, Emily; Visvanathan, Kala; Jones, Miranda R.; Relton, Caroline; Brennan, Paul; Johansson, Mattias; Ulvik, Arve.

In: International Journal of Cancer, Vol. 142, No. 12, 15.06.2018, p. 2425-2434.

Research output: Contribution to journalArticle

Theofylaktopoulou, D, Midttun, Ø, Ueland, PM, Meyer, K, Fanidi, A, Zheng, W, Shu, XO, Xiang, YB, Prentice, R, Pettinger, M, Thomson, CA, Giles, GG, Hodge, A, Cai, Q, Blot, WJ, Wu, J, Johansson, M, Hultdin, J, Grankvist, K, Stevens, VL, McCullough, MM, Weinstein, SJ, Albanes, D, Ziegler, R, Freedman, ND, Langhammer, A, Hveem, K, Næss, M, Sesso, HD, Gaziano, JM, Buring, JE, Lee, IM, Severi, G, Zhang, X, Stampfer, MJ, Han, J, Smith-Warner, SA, Zeleniuch-Jacquotte, A, Le Marchand, L, Yuan, JM, Wang, R, Butler, LM, Koh, WP, Gao, YT, Rothman, N, Ericson, U, Sonestedt, E, Visvanathan, K, Jones, MR, Relton, C, Brennan, P, Johansson, M & Ulvik, A 2018, 'Impaired functional vitamin B6 status is associated with increased risk of lung cancer', International Journal of Cancer, vol. 142, no. 12, pp. 2425-2434. https://doi.org/10.1002/ijc.31215
Theofylaktopoulou D, Midttun Ø, Ueland PM, Meyer K, Fanidi A, Zheng W et al. Impaired functional vitamin B6 status is associated with increased risk of lung cancer. International Journal of Cancer. 2018 Jun 15;142(12):2425-2434. https://doi.org/10.1002/ijc.31215
Theofylaktopoulou, Despoina ; Midttun, Øivind ; Ueland, Per M. ; Meyer, Klaus ; Fanidi, Anouar ; Zheng, Wei ; Shu, Xiao Ou ; Xiang, Yong Bing ; Prentice, Ross ; Pettinger, Mary ; Thomson, Cynthia A. ; Giles, Graham G. ; Hodge, Allison ; Cai, Qiuyin ; Blot, William J. ; Wu, Jie ; Johansson, Mikael ; Hultdin, Johan ; Grankvist, Kjell ; Stevens, Victoria L. ; McCullough, Marjorie M. ; Weinstein, Stephanie J. ; Albanes, Demetrius ; Ziegler, Regina ; Freedman, Neal D. ; Langhammer, Arnulf ; Hveem, Kristian ; Næss, Marit ; Sesso, Howard D. ; Gaziano, J. Michael ; Buring, Julie E. ; Lee, I. Min ; Severi, Gianluca ; Zhang, Xuehong ; Stampfer, Meir J. ; Han, Jiali ; Smith-Warner, Stephanie A. ; Zeleniuch-Jacquotte, Anne ; Le Marchand, Loic ; Yuan, Jian Min ; Wang, Renwei ; Butler, Lesley M. ; Koh, Woon Puay ; Gao, Yu Tang ; Rothman, Nathaniel ; Ericson, Ulrika ; Sonestedt, Emily ; Visvanathan, Kala ; Jones, Miranda R. ; Relton, Caroline ; Brennan, Paul ; Johansson, Mattias ; Ulvik, Arve. / Impaired functional vitamin B6 status is associated with increased risk of lung cancer. In: International Journal of Cancer. 2018 ; Vol. 142, No. 12. pp. 2425-2434.
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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 (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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AU - Fanidi, Anouar

AU - Zheng, Wei

AU - Shu, Xiao Ou

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AU - Albanes, Demetrius

AU - Ziegler, Regina

AU - Freedman, Neal D.

AU - Langhammer, Arnulf

AU - Hveem, Kristian

AU - Næss, Marit

AU - Sesso, Howard D.

AU - Gaziano, J. Michael

AU - Buring, Julie E.

AU - Lee, I. Min

AU - Severi, Gianluca

AU - Zhang, Xuehong

AU - Stampfer, Meir J.

AU - Han, Jiali

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AU - Koh, Woon Puay

AU - Gao, Yu Tang

AU - Rothman, Nathaniel

AU - Ericson, Ulrika

AU - Sonestedt, Emily

AU - Visvanathan, Kala

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