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

Valéria Troncoso Baltar, 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 GilsN 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

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)677-88
Number of pages12
JournalEuropean Journal of Epidemiology
Volume28
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Biological Markers
  • Folic Acid
  • Humans
  • Lung Neoplasms
  • Male
  • Methionine
  • Models, Statistical
  • Population Surveillance
  • Prospective Studies
  • Risk Factors
  • Vitamin B Complex

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