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European Journal of Epidemiology

, Volume 28, Issue 8, pp 677–688 | Cite as

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

  • Valéria Troncoso BaltarEmail author
  • Wei W. Xun
  • Mattias Johansson
  • Pietro Ferrari
  • Shu-Chun Chuang
  • Caroline Relton
  • Per Magne Ueland
  • Øivind Midttun
  • Nadia Slimani
  • Mazda Jenab
  • Françoise Clavel-Chapelon
  • Marie-Christine Boutron-Ruault
  • Guy Fagherazzi
  • Rudolf Kaaks
  • Sabine Rohrmann
  • Heiner Boeing
  • Cornelia Weikert
  • Bas Bueno-de-Mesquita
  • Hendriek Boshuizen
  • Carla H. van Gils
  • N. Charlotte Onland-Moret
  • Antonio Agudo
  • Aurelio Barricarte
  • Carmen Navarro
  • Laudina Rodríguez
  • José Maria Huerta Castaño
  • Nerea Larrañaga
  • Kay-Tee Khaw
  • Nick Wareham
  • Naomi E. Allen
  • Francesca Crowe
  • Valentina Gallo
  • Teresa Norat
  • Vittorio Krogh
  • Giovanna Masala
  • Salvatore Panico
  • Carlotta Sacerdote
  • Rosario Tumino
  • Antonia Trichopoulou
  • Pagona Lagiou
  • Dimitrios Trichopoulos
  • Torgny Rasmuson
  • Göran Hallmans
  • Nina Roswall
  • Anne Tjønneland
  • Elio Riboli
  • Paul Brennan
  • Paolo Vineis
CANCER

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.

Keywords

B vitamins Folate Methionine Lung cancer Immune markers Structural equation model 

Notes

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.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Valéria Troncoso Baltar
    • 1
    • 2
    Email author
  • Wei W. Xun
    • 2
  • Mattias Johansson
    • 3
  • Pietro Ferrari
    • 3
  • Shu-Chun Chuang
    • 2
  • Caroline Relton
    • 4
  • Per Magne Ueland
    • 5
    • 6
  • Øivind Midttun
    • 7
  • Nadia Slimani
    • 3
  • Mazda Jenab
    • 3
  • Françoise Clavel-Chapelon
    • 8
    • 9
    • 10
  • Marie-Christine Boutron-Ruault
    • 8
    • 9
    • 10
  • Guy Fagherazzi
    • 8
    • 9
    • 10
  • Rudolf Kaaks
    • 11
  • Sabine Rohrmann
    • 12
  • Heiner Boeing
    • 13
  • Cornelia Weikert
    • 13
  • Bas Bueno-de-Mesquita
    • 14
  • Hendriek Boshuizen
    • 15
  • Carla H. van Gils
    • 16
  • N. Charlotte Onland-Moret
    • 16
  • Antonio Agudo
    • 17
  • Aurelio Barricarte
    • 18
    • 22
  • Carmen Navarro
    • 19
    • 22
  • Laudina Rodríguez
    • 20
  • José Maria Huerta Castaño
    • 21
    • 22
  • Nerea Larrañaga
    • 22
    • 23
  • Kay-Tee Khaw
    • 24
  • Nick Wareham
    • 25
  • Naomi E. Allen
    • 26
  • Francesca Crowe
    • 26
  • Valentina Gallo
    • 2
  • Teresa Norat
    • 2
  • Vittorio Krogh
    • 27
  • Giovanna Masala
    • 28
  • Salvatore Panico
    • 29
  • Carlotta Sacerdote
    • 30
  • Rosario Tumino
    • 31
  • Antonia Trichopoulou
    • 32
    • 33
  • Pagona Lagiou
    • 32
    • 34
  • Dimitrios Trichopoulos
    • 34
    • 35
  • Torgny Rasmuson
    • 36
  • Göran Hallmans
    • 37
  • Nina Roswall
    • 38
  • Anne Tjønneland
    • 38
  • Elio Riboli
    • 2
  • Paul Brennan
    • 3
  • Paolo Vineis
    • 30
    • 39
  1. 1.Department of Epidemiology, Faculty of Public HealthUniversity of São PauloSão PauloBrazil
  2. 2.Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public HealthImperial College LondonLondonUK
  3. 3.International Agency for Research on CancerLyonFrance
  4. 4.Institute for Ageing and Health, Newcastle University, Campus for Ageing and VitalityNewcastleUK
  5. 5.Section for Pharmacology, Institute of MedicineUniversity of BergenBergenNorway
  6. 6.Haukeland University HospitalBergenNorway
  7. 7.Bevital ASBergenNorway
  8. 8.Institut National de la Santé et de la Recherche Médicale (INSERM) U780-IFR169VillejuifFrance
  9. 9.Institut Gustave RoussyVillejuifFrance
  10. 10.Paris South UniversityVillejuifFrance
  11. 11.Division of Cancer EpidemiologyGerman Cancer Research CentreHeidelbergGermany
  12. 12.Division of Clinical EpidemiologyGerman Cancer Research CentreHeidelbergGermany
  13. 13.Department of EpidemiologyGerman Institute of Human NutritionNuthetalGermany
  14. 14.Department for Determinants of Chronic DiseasesNational Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands
  15. 15.Department of EpidemiologyNational Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands
  16. 16.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands
  17. 17.Unit of Nutrition, Environment and Cancer, Catalan Institute of OncologyL’Hospitalet de LlobregatBarcelonaSpain
  18. 18.Epidemiology, Prevention and Promotion Health ServicePublic Health Institute of NavarraNavarraSpain
  19. 19.Department of EpidemiologyRegional Council of Health and Consumer AffairsMurciaSpain
  20. 20.Public Health and Participation DirectorateHealth and Health Care Services CouncilAsturiasSpain
  21. 21.Department of EpidemiologyMurcia Regional Health AuthorityMurciaSpain
  22. 22.CIBER of Epidemiology and Public HealthBarcelonaSpain
  23. 23.Epidemiology Unit, Public Health Department of GipuzkoaBasque GovernmentSan SebastiánSpain
  24. 24.Clinical Gerontology Unit, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  25. 25.MRC Epidemiology Unit, Strangeways Research LaboratoryCambridgeUK
  26. 26.Cancer Epidemiology UnitUniversity of OxfordOxfordUK
  27. 27.Nutritional Epidemiology Unit, National Cancer InstituteMilanItaly
  28. 28.Molecular and Nutritional Epidemiology Unit, ISPO—Cancer Research and Prevention InstituteFlorenceItaly
  29. 29.Department of Clinical and Experimental MedicineFederico II University of NaplesNaplesItaly
  30. 30.Human Genetics Foundation (HuGeF)TurinItaly
  31. 31.Cancer Registry and Histopathology Unit“Civile M.P.Arezzo” HospitalRagusaItaly
  32. 32.Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition PoliciesUniversity of Athens Medical SchoolAthensGreece
  33. 33.Hellenic Health FoundationAthensGreece
  34. 34.Department of Epidemiology, Harvard School of Public HealthHarvard UniversityBostonUSA
  35. 35.Bureau of Epidemiologic ResearchAcademy of AthensAthensGreece
  36. 36.Department of Radiation Sciences, OncologyUmeå UniversityUmeåSweden
  37. 37.Department of Public Health and Clinical MedicineUmeå UniversityUmeåSweden
  38. 38.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark
  39. 39.Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and HealthImperial College LondonLondonUK

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