TY - JOUR
T1 - Impaired functional vitamin B6 status is associated with increased risk of lung cancer
AU - Theofylaktopoulou, Despoina
AU - Midttun, Øivind
AU - Ueland, Per M.
AU - Meyer, Klaus
AU - Fanidi, Anouar
AU - Zheng, Wei
AU - Shu, Xiao Ou
AU - Xiang, Yong Bing
AU - Prentice, Ross
AU - Pettinger, Mary
AU - Thomson, Cynthia A.
AU - Giles, Graham G.
AU - Hodge, Allison
AU - Cai, Qiuyin
AU - Blot, William J.
AU - Wu, Jie
AU - Johansson, Mikael
AU - Hultdin, Johan
AU - Grankvist, Kjell
AU - Stevens, Victoria L.
AU - McCullough, Marjorie M.
AU - Weinstein, Stephanie J.
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
AU - Smith-Warner, Stephanie A.
AU - Zeleniuch-Jacquotte, Anne
AU - Le Marchand, Loic
AU - Yuan, Jian Min
AU - Wang, Renwei
AU - Butler, Lesley M.
AU - Koh, Woon Puay
AU - Gao, Yu Tang
AU - Rothman, Nathaniel
AU - Ericson, Ulrika
AU - Sonestedt, Emily
AU - Visvanathan, Kala
AU - Jones, Miranda R.
AU - Relton, Caroline
AU - Brennan, Paul
AU - Johansson, Mattias
AU - Ulvik, Arve
N1 - Funding Information:
Key words: pyridoxal 5′-phosphate, functional vitamin B6 marker, 3-hydroxykynurenine:xanthurenic acid, Lung Cancer Cohort Consortium Abbreviations: ATBC: alpha-tocopherol, beta-carotene cancer prevention; CI: confidence interval; EPIC: European Prospective Investigation into Cancer and Nutrition; HK:XA: 3-hydroxykynurenine:xanthurenic acid; LC3: Lung Cancer Cohort Consortium; PLP: pyridoxal 5′-phosphate; OR: odds ratio Additional Supporting Information may be found in the online version of this article. Conflict of interest: L.M.B. is an employee of Genetech Inc. as of September 16. Grant sponsor: NIH/NCI; Grant number: 1U01CA155340-01; Grant sponsor: Australian National Health and Medical Research Committee; Grant number: 1050198; Grant sponsor: National Cancer Institute; Grant numbers: R37 CA070867, UM1 CA182910, R01 CA082729, UM1 CA173640, R01 CA092447, U01 CA202979, U01 CA164973; Grant sponsors: National Institutes of Health, National Cancer Institute, Department of Health and Human Services, the State of Maryland, the Maryland Cigarette Restitution Fund, the National Program of Cancer Registries of the Centers for Disease Control and Prevention, Division of Cancer Prevention, Division of Cancer Epidemiology and Genetics, U.S. National Institutes of Health (NIH); Grant numbers: UM1CA167552, UM1CA186107, P01CA87969, R01CA49449; Grant sponsor: CRUK; Grant number: C18281/A19169; Grant sponsor: MRC; Grant number: MC_UU_12013/2; Grant sponsor: University of Bristol DOI: 10.1002/ijc.31215 History: Received 1 Aug 2017; Accepted 22 Nov 2017; Online 14 Dec 2017 Correspondence to: Øivind Midttun, Post Box 7804, 5020 Bergen, Norway, E-mail: Bjorn.Midttun@uib.no; Tel: 147 55 97 46 04
Funding Information:
The Lung Cancer Cohort Consortium (LC3) was supported by NIH/NCI grant 1U01CA155340-01 and Australian National Health and Medical Research Committee grant 1050198. SWHS was/is supported by R37 CA070867 and UM1 CA182910, SMHS by R01 CA082729 and UM1 CA173640 from the U.S. National Cancer Institute. SCCS is supported by R01 CA092447 and U01 CA202979 from the U.S. National Cancer Institute. The Multiethnic Cohort Study was funded in part by grant U01 CA164973. The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services. CLUE thank the participants and staff for their contributions, as well as the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, 201W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/cancer, 410–767-4055. CLUE acknowledges the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data. The Prostate Lung Colorectal Ovarian Cancer Screening Trial (PLCO) is supported by contracts from the Division of Cancer Prevention and intramural research funding from the Division of Cancer Epidemiology and Genetics, National Cancer Institute, U.S. National Institutes of Health (NIH), Department of Health and Human Services (DHHS). PLCO was supported by the National Institutes of Health (NIH) grants, UM1CA167552, UM1CA186107, P01CA87969 and R01CA49449. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. C.R. is supported by CRUK (C18281/A19169) and the Medical Research Council Integrative Epidemiology Unit at the University of Bristol with funds from the MRC (MC_UU_12013/2) and the University of Bristol. The funding organizations had no role in design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the article.
Publisher Copyright:
© 2017 UICC
PY - 2018/6/15
Y1 - 2018/6/15
N2 - 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.
AB - 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.
KW - 3-hydroxykynurenine:xanthurenic acid
KW - Lung Cancer Cohort Consortium
KW - functional vitamin B6 marker
KW - pyridoxal 5′-phosphate
UR - http://www.scopus.com/inward/record.url?scp=85045757473&partnerID=8YFLogxK
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U2 - 10.1002/ijc.31215
DO - 10.1002/ijc.31215
M3 - Article
C2 - 29238985
AN - SCOPUS:85045757473
SN - 0020-7136
VL - 142
SP - 2425
EP - 2434
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -