Results from the European prospective investigation into cancer and nutrition link vitamin B6 catabolism and lung cancer risk
Zuo, Hui; Ueland, Per Magne; Midttun, Øivind; Vollset, Stein Emil; Tell, Grethe S.; Theofylaktopoulou, Despoina; Travis, Ruth C.; Boutron-Ruault, Marie Christine; Fournier, Agnès; Severi, Gianluca; Kvaskoff, Marina; Boeing, Heiner; Bergmann, Manuela M.; Turzanski-Fortner, Renée; Kaaks, Rudolf; Trichopoulou, Antonia; Kotanidou, Anastasia; Lagiou, Pagona; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Bueno-De-Mesquita, H. Bas; Peeters, Petra H.; Grankvist, Kjell; Johansson, Mikael; Agudo, Antonio; Garcia, Jose Ramon Quiros; Larranaga, Nerea; Sanchez, Maria-Jose; Chirlaque, Maria-Dolores; Ardanaz, Eva; Chuang, Shu Chun; Gallo, Valentina; Brennan, Paul; Johansson, Mattias; Ulvik, Arve
(2018) Cancer Research, volume 78, issue 1, pp. 302 - 308
(Article)
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
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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 vitaminB6 levels with lung cancer risk.
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Keywords: Oncology, Cancer Research
ISSN: 0008-5472
Publisher: American Association for Cancer Research Inc.
Note: Funding Information: The EPIC study (all authors) has been supported by the Europe Against Cancer Program of the European Commission (SANCO); Deutsche Kreb-shilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology; the Red Temática de Investigación Cooperativa en Cáncer of the Instituto de Salud Carlos III (ISCIII RTICC RD12/0036/0018), cofounded by FEDER funds/European Regional Development Fund (ERDF); Cancer Research UK; Medical Research Council, United Kingdom; Greek Ministry of Health; Stavros Niarchos Foundation; Hellenic Health Foundation; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Associazione Italiana per la Ricerca sul Cancro (AIRC-Milan); Compagnia di San Paolo, Italy; Dutch Ministry of Public Health, Welfare, and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (the Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of V€asterbotten, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Générale de l'Éducation Nationale (MGEN), France; 3M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France. This work was supported by World Cancer Research Fund (principal investigator: P.J. Brennan) and the Foundation to Promote Research into Functional Vitamin B12-Deficiency (principal investigator: P.M. Ueland). Publisher Copyright: © 2017 American Association for Cancer Research.
(Peer reviewed)