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A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk

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Abstract

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

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Acknowledgments

This paper was supported by the World Cancer Research Fund (grant number 2007/16-UK). This paper forms part of VTB’s Ph.D. Dissertation. VTB was supported by the National Council for Scientific, Technological Development (CNPq) and Capes Foundation, Brazil.

Conflict of interests

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Faculty of Public Health, University of São Paulo, Av. Dr Arnaldo, 715, São Paulo, São Paulo, CEP 01246-904, Brazil

    Valéria Troncoso Baltar

  2. Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK

    Valéria Troncoso Baltar, Wei W. Xun, Shu-Chun Chuang, Valentina Gallo, Teresa Norat & Elio Riboli

  3. International Agency for Research on Cancer, Lyon, France

    Mattias Johansson, Pietro Ferrari, Nadia Slimani, Mazda Jenab & Paul Brennan

  4. Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle, UK

    Caroline Relton

  5. Section for Pharmacology, Institute of Medicine, University of Bergen, Bergen, Norway

    Per Magne Ueland

  6. Haukeland University Hospital, Bergen, Norway

    Per Magne Ueland

  7. Bevital AS, Bergen, Norway

    Øivind Midttun

  8. Institut National de la Santé et de la Recherche Médicale (INSERM) U780-IFR169, Villejuif, France

    Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault & Guy Fagherazzi

  9. Institut Gustave Roussy, Villejuif, France

    Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault & Guy Fagherazzi

  10. Paris South University, Villejuif, France

    Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault & Guy Fagherazzi

  11. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany

    Rudolf Kaaks

  12. Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany

    Sabine Rohrmann

  13. Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany

    Heiner Boeing & Cornelia Weikert

  14. Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    Bas Bueno-de-Mesquita

  15. Department of Epidemiology, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    Hendriek Boshuizen

  16. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Carla H. van Gils & N. Charlotte Onland-Moret

  17. Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain

    Antonio Agudo

  18. Epidemiology, Prevention and Promotion Health Service, Public Health Institute of Navarra, Navarra, Spain

    Aurelio Barricarte

  19. Department of Epidemiology, Regional Council of Health and Consumer Affairs, Murcia, Spain

    Carmen Navarro

  20. Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain

    Laudina Rodríguez

  21. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain

    José Maria Huerta Castaño

  22. CIBER of Epidemiology and Public Health, Barcelona, Spain

    Aurelio Barricarte, Carmen Navarro, José Maria Huerta Castaño & Nerea Larrañaga

  23. Epidemiology Unit, Public Health Department of Gipuzkoa, Basque Government, San Sebastián, Spain

    Nerea Larrañaga

  24. Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Kay-Tee Khaw

  25. MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK

    Nick Wareham

  26. Cancer Epidemiology Unit, University of Oxford, Oxford, UK

    Naomi E. Allen & Francesca Crowe

  27. Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy

    Vittorio Krogh

  28. Molecular and Nutritional Epidemiology Unit, ISPO—Cancer Research and Prevention Institute, Florence, Italy

    Giovanna Masala

  29. Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy

    Salvatore Panico

  30. Human Genetics Foundation (HuGeF), Turin, Italy

    Carlotta Sacerdote & Paolo Vineis

  31. Cancer Registry and Histopathology Unit, “Civile M.P.Arezzo” Hospital, ASP 7, Ragusa, Italy

    Rosario Tumino

  32. Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece

    Antonia Trichopoulou & Pagona Lagiou

  33. Hellenic Health Foundation, Athens, Greece

    Antonia Trichopoulou

  34. Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA

    Pagona Lagiou & Dimitrios Trichopoulos

  35. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece

    Dimitrios Trichopoulos

  36. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

    Torgny Rasmuson

  37. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    Göran Hallmans

  38. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark

    Nina Roswall & Anne Tjønneland

  39. Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London, UK

    Paolo Vineis

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  1. Valéria Troncoso Baltar
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Correspondence to Valéria Troncoso Baltar.

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Baltar, V.T., Xun, W.W., Johansson, M. et al. A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk. Eur J Epidemiol 28, 677–688 (2013). https://doi.org/10.1007/s10654-013-9793-z

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