H Zuo1, P M Ueland2, Ø Midttun3, G S Tell4, A Fanidi5, W Zheng6, X Shu6, Y Xiang7, J Wu6, R Prentice8, M Pettinger8, C A Thomson9, G G Giles10, A Hodge10, Q Cai6, W J Blot6, M Johansson31, J Hultdin12, K Grankvist12, V L Stevens13, M L McCullough13, S J Weinstein14, D Albanes14, R G Ziegler14, N D Freedman14, N E Caporaso14, A Langhammer15, K Hveem15, M Næss15, J E Buring16, I Lee16, J M Gaziano17, G Severi18, X Zhang19, M J Stampfer20, J Han21, A Zeleniuch-Jacquotte22, L L Marchand23, J Yuan24, R Wang25, W Koh26, Y Gao27, U Ericson28, K Visvanathan29, M R Jones29, C Relton30, P Brennan31, M Johansson31, A Ulvik3. 1. Department of Global Public Health and Primary Care, University of Bergen, Bergen. Electronic address: hui.zuo@uib.no. 2. Department of Clinical Science, University of Bergen, Bergen; Laboratory of Medicine and Pathology, Haukeland University Hospital, Bergen. 3. Bevital AS, Bergen, Norway. 4. Department of Global Public Health and Primary Care, University of Bergen, Bergen. 5. Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France; MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. 6. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, USA. 7. State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 8. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle. 9. Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, USA. 10. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. 11. Department of Radiation Sciences, Oncology, Umeå University, Umeå. 12. Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden. 13. Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta. 14. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA. 15. HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Science, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. 16. Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston. 17. Division of Aging, Brigham and Women's Hospital, Boston; VA Boston Healthcare System, Boston, USA. 18. Human Genetics Foundation (HuGeF), Torin, Italy; CESP (U1018 INSERM), Université Paris-Saclay, USQ, Villejuif, France. 19. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. 20. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston. 21. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis. 22. Department of Population Health, New York University School of Medicine, New York. 23. Epidemiology Program, University of Hawaii Cancer Center, Honolulu. 24. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, USA. 25. Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh. 26. Duke-NUS Medical School, Singapore and Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. 27. Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, China. 28. Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. 29. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Johns Hopkins Sidney Kimmel Comprehensive Center, School of Medicine, Baltimore, USA. 30. Institute of Genetic Medicine, Newcastle University, Newcastle; MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, UK. 31. Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
Abstract
BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS:PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
Authors: Hana Zahed; Mattias Johansson; Per M Ueland; Øivind Midttun; Roger L Milne; Graham G Giles; Jonas Manjer; Malte Sandsveden; Arnulf Langhammer; Elin Pettersen Sørgjerd; Kjell Grankvist; Mikael Johansson; Neal D Freedman; Wen-Yi Huang; Chu Chen; Ross Prentice; Victoria L Stevens; Ying Wang; Loic Le Marchand; Lynne R Wilkens; Stephanie J Weinstein; Demetrius Albanes; Qiuyin Cai; William J Blot; Alan A Arslan; Anne Zeleniuch-Jacquotte; Xiao-Ou Shu; Wei Zheng; Jian-Min Yuan; Woon-Puay Koh; Kala Visvanathan; Howard D Sesso; Xuehong Zhang; J Michael Gaziano; Anouar Fanidi; David Muller; Paul Brennan; Florence Guida; Hilary A Robbins Journal: Sci Rep Date: 2021-07-05 Impact factor: 4.996