TY - JOUR
T1 - A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk
AU - Baltar, Valéria Troncoso
AU - Xun, Wei W.
AU - Johansson, Mattias
AU - Ferrari, Pietro
AU - Chuang, Shu Chun
AU - Relton, Caroline
AU - Ueland, Per Magne
AU - Midttun, Øivind
AU - Slimani, Nadia
AU - Jenab, Mazda
AU - Clavel-Chapelon, Françoise
AU - Boutron-Ruault, Marie Christine
AU - Fagherazzi, Guy
AU - Kaaks, Rudolf
AU - Rohrmann, Sabine
AU - Boeing, Heiner
AU - Weikert, Cornelia
AU - Bueno-De-Mesquita, Bas
AU - Boshuizen, Hendriek
AU - Van Gils, Carla H.
AU - Onland-Moret, N. Charlotte
AU - Agudo, Antonio
AU - Barricarte, Aurelio
AU - Navarro, Carmen
AU - Rodríguez, Laudina
AU - Castaño, José Maria Huerta
AU - Larrañaga, Nerea
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Allen, Naomi E.
AU - Crowe, Francesca
AU - Gallo, Valentina
AU - Norat, Teresa
AU - Krogh, Vittorio
AU - Masala, Giovanna
AU - Panico, Salvatore
AU - Sacerdote, Carlotta
AU - Tumino, Rosario
AU - Trichopoulou, Antonia
AU - Lagiou, Pagona
AU - Trichopoulos, Dimitrios
AU - Rasmuson, Torgny
AU - Hallmans, Göran
AU - Roswall, Nina
AU - Tjønneland, Anne
AU - Riboli, Elio
AU - Brennan, Paul
AU - Vineis, Paolo
N1 - Funding Information:
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.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - B vitamins
KW - Folate
KW - Immune markers
KW - Lung cancer
KW - Methionine
KW - Structural equation model
UR - http://www.scopus.com/inward/record.url?scp=84884354784&partnerID=8YFLogxK
U2 - 10.1007/s10654-013-9793-z
DO - 10.1007/s10654-013-9793-z
M3 - Article
C2 - 23532743
AN - SCOPUS:84884354784
SN - 0393-2990
VL - 28
SP - 677
EP - 688
JO - European Journal of Epidemiology
JF - European Journal of Epidemiology
IS - 8
ER -