title: The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study.
abstract: Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.
authors.affiliation: Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Carreras-Torres
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Haycock
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.|National Institute for Health Research Biomedical Research Unit in Nutrition, Diet and Lifestyle at University Hospitals Bristol NHS Foundation Trust and the University of Bristol, BS2 8AE, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Tworoger
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Sungshim L
authors.initials: SL
authors.lastname: Park
authors.affiliation: Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Haiman
authors.affiliation: Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK.
authors.forename: John K
authors.initials: JK
authors.lastname: Field
authors.affiliation: Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Davies
authors.affiliation: Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Marcus
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Center, Toronto, ON, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Genetic Epidemiology Branch, DCEG, National Cancer Institute, NIH, Rockville, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Departments of Environmental Health and Epidemiology, Harvard T. H. Chan School of Public Health and Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Departments of Environmental Health and Epidemiology, Harvard T. H. Chan School of Public Health and Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, USA.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Goodman
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Department of Biomedical Data Science, Geisel School of medicine, Dartmouth College, Lebanon, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: James
authors.initials: J
authors.lastname: McKay
authors.affiliation: Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods; D012307:Risk Factors; D012907:Smoking / Q000473:pathology