title: A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.
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.
authors.affiliation: Department of Epidemiology, Faculty of Public Health, University of São Paulo, Av. Dr Arnaldo, 715, São Paulo, São Paulo, CEP 01246-904, Brazil, vbaltar@usp.br.
authors.forename: Valéria Troncoso
authors.initials: VT
authors.lastname: Baltar
authors.forename: Wei W
authors.initials: WW
authors.lastname: Xun
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Chuang
authors.forename: Caroline
authors.initials: C
authors.lastname: Relton
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Guy
authors.initials: G
authors.lastname: Fagherazzi
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Sabine
authors.initials: S
authors.lastname: Rohrmann
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: Bas
authors.initials: B
authors.lastname: Bueno-de-Mesquita
authors.forename: Hendriek
authors.initials: H
authors.lastname: Boshuizen
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodríguez
authors.forename: José Maria Huerta
authors.initials: JM
authors.lastname: Castaño
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Francesca
authors.initials: F
authors.lastname: Crowe
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Torgny
authors.initials: T
authors.lastname: Rasmuson
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Nina
authors.initials: N
authors.lastname: Roswall
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D015415:Biomarkers / Q000097:blood*; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000097:blood; D015233:Models, Statistical; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood*
chemical_list: D015415:Biomarkers; D014803:Vitamin B Complex; D005492:Folic Acid; D008715:Methionine