title: Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer.
abstract: BACKGROUND
  Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC.
  
  
  METHODS
  We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls.
  
  
  RESULTS
  In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02-1.49, P=0.033), 1.59 (95% CI: 1.08-2.34, P=0.019) and 1.07 (95% CI: 1.03-1.13, P=0.018), respectively. There was no evidence for association between birth weight and CRC (OR=1.22, 95% CI: 0.89-1.67, P=0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10-1.44, P=7.7 × 10(-4)) and 1.40 (95% CI: 1.14-1.72, P=1.2 × 10(-3)), respectively.
  
  
  CONCLUSIONS
  These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: David
authors.initials: D
authors.lastname: Jarvis
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Mitchell
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Law
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Palin
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Tuupanen
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gylfe
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Ulrika A
authors.initials: UA
authors.lastname: Hänninen
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cajuso
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Tomas
authors.initials: T
authors.lastname: Tanskanen
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Kondelin
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Eevi
authors.initials: E
authors.lastname: Kaasinen
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.|National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.|Folkhälsan Research Centre, Helsinki 00250, Finland.|Unit of General Practice and Primary Health Care, University of Helsinki, Helsinki University Hospital, Helsinki 00014, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Rissanen
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Paul
authors.initials: P
authors.lastname: Knekt
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki 00130, Finland.|School of Health Sciences, University of Tampere, Tampere 33014, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.|Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.|Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.|Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Department of Surgery, Helsinki University Central Hospital, Hospital District of Helsinki and Uusimaa, Helsinki 00029, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Järvinen
authors.affiliation: Department of Surgery, Abdominal Center, Helsinki University Hospital Helsinki 00029, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Renkonen-Sinisalo
authors.affiliation: Department of Surgery, Abdominal Center, Helsinki University Hospital Helsinki 00029, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lepistö
authors.affiliation: Department of Pathology, Central Finland Central Hospital, Jyväskylä 40620, Finland.
authors.forename: Jan
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Department of Surgery, Jyväskylä Central Hospital, University of Eastern Finland, Jyväskylä 40620, Finland.
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Meklin
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia.
authors.forename: Nada A
authors.initials: NA
authors.lastname: Al-Tassan
authors.affiliation: Wellcome Trust Centre for Human Genetics, NIHR Comprehensive Biomedical Research Centre, Oxford OX3 7BN, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Palles
authors.affiliation: Wellcome Trust Centre for Human Genetics, NIHR Comprehensive Biomedical Research Centre, Oxford OX3 7BN, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.affiliation: Wellcome Trust Centre for Human Genetics, NIHR Comprehensive Biomedical Research Centre, Oxford OX3 7BN, UK.
authors.forename: Ella
authors.initials: E
authors.lastname: Barclay
authors.affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.|The Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Edinburgh EH25 9RG, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Timofeeva
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Smith
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Shelley
authors.initials: S
authors.lastname: Idziaszczyk
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Maughan
authors.affiliation: MRC Clinical Trials Unit, Aviation House, London WC2B 6NH, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Kaplan
authors.affiliation: Department of Oncology, Oxford Cancer Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kerr
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: David
authors.initials: D
authors.lastname: Kerr
authors.affiliation: Department of Pathology, Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, The University of Melbourne, Melbourne, VIC 3010, Australia.|Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Aung K
authors.initials: AK
authors.lastname: Win
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ 85259, USA.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: David
authors.initials: D
authors.lastname: Conti
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.|Department of Biosciences and Nutrition, SciLife Center, Karolinska Institutet, Solna SE 141 83, Sweden.
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki 00014, Helsinki, Finland.|Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Cheadle
authors.affiliation: Colon Cancer Genetics Group, MRC Human Genetics Unit, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.affiliation: Wellcome Trust Centre for Human Genetics, NIHR Comprehensive Biomedical Research Centre, Oxford OX3 7BN, UK.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Tomlinson
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D015179:Colorectal Neoplasms / Q000150:complications* / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation