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Results from the European Prospective Investigation into Cancer and Nutrition Link Vitamin B6 Catabolism and Lung Cancer Risk

Zuo H 1 , Ueland PM 2 , Midttun Ø 3 , Vollset SE 4 , Tell GS 4 , Theofylaktopoulou D 2 Show all authors , Travis RC 5 , Boutron-Ruault MC 6 , Fournier A 6 , Severi G 6 , Kvaskoff M 6 , Boeing H 7 , Bergmann MM 7 , Fortner RT 8 , Kaaks R 8 , Trichopoulou A 9 , Kotanidou A 10 , Lagiou P 9 , Palli D 11 , Sieri S 12 , Panico S 13 , Bueno-de-Mesquita HB 14 , Peeters PH 15 , Grankvist K 16 , Johansson M 17 , Agudo A 18 , Garcia JRQ 19 , Larranaga N 20 , Sanchez MJ 20 , Chirlaque MD 20 , Ardanaz E 20 , Chuang SC 21 , Gallo V 22 , Brennan P 23 , Johansson M 23 , Ulvik A 3

Affiliations 

  • 1 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. hui.zuo@uib.no
  • 2 Department of Clinical Science, University of Bergen, Bergen, Norway
  • 3 Bevital A/S, Bergen, Norway
  • 4 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  • 5 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
  • 6 Université Paris-Saclay, Université Paris-Sud, UVSQ, Inserm, CESP, Generations and health, Gustave Roussy, Villejuif, France
  • 7 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Germany
  • 8 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 9 Hellenic Health Foundation, Athens, Greece
  • 10 First Department of Critical Care Medicine and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece
  • 11 Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
  • 12 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, Milano, Italy
  • 13 Dipartimento di Medicina Clinica Echirurgia Federico II University, Naples, Italy
  • 14 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 15 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  • 16 Department of Medical Biosciences, Umeå University, Umeå, Sweden
  • 17 Department of Radiation Sciences, Umeå University, Umeå, Sweden
  • 18 Unic of Nutrition and Cancer, Cataln Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Spain
  • 19 Public Health Directorate, Asturias, Spain
  • 20 CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
  • 21 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan
  • 22 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
  • 23 International Agency for Research on Cancer, Lyon, France
Cancer Res, 2018 Jan 01;78(1):302-308.
PMID: 29070616 DOI: 10.1158/0008-5472.CAN-17-1923

Abstract

Circulating pyridoxal-5'-phosphate (PLP) has been linked to lung cancer risk. The PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects increased vitamin B6 catabolism during inflammation. PAr has been defined as a marker of lung cancer risk in a prospective cohort study, but analysis of a larger numbers of cases are needed to deepen the significance of this study. Here, we conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892 incident lung cancer cases and 1,748 controls matched by center, gender, date of blood collection, and date of birth. The association of PAr with risk of lung cancer was evaluated by using conditional logistic regression. Study participants with elevated PAr experienced higher risk of lung cancer in a dose-response fashion, with a doubling in PAr levels associated with 52% higher odds of lung cancer after adjustment for tobacco smoking, serum cotinine levels, educational attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27-1.81; P < 0.001]. Additional adjustment for intake of vegetables and fruits and physical activity did not materially affect risk association. The association of PAr with lung cancer risk was similar in both genders but slightly stronger in former smokers and in participants diagnosed with squamous cell carcinoma. This study provides robust evidence that increased vitamin B6 catabolism is independently associated with a higher risk of future lung cancer.Significance: This large cohort study firmly establishes an association between an index of vitamin B6 levels with lung cancer risk. Cancer Res; 78(1); 302-8. ©2017 AACR.

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