Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer

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Jarvis , D , Mitchell , J S , Law , P J , Palin , K , Tuupanen , S , Gylfe , A , Hanninen , U A , Cajuso , T , Tanskanen , T , Kondelin , J , Kaasinen , E , Sarin , A-P , Kaprio , J , Eriksson , J G , Rissanen , H , Knekt , P , Pukkala , E , Jousilahti , P , Salomaa , V , Ripatti , S , Palotie , A , Järvinen , H , Renkonen-Sinisalo , L , Lepistö , A , Bohm , J , Mecklin , J-P , Al-Tassan , N A , Palles , C , Martin , L , Barclay , E , Farrington , S M , Timofeeva , M N , Meyer , B F , Wakil , S M , Campbell , H , Smith , C G , Idziaszczyk , S , Maughan , T S , Kaplan , R , Kerr , R , Kerr , D , Buchanan , D D , Win , A K , Hopper , J L , Jenkins , M A , Lindor , N M , Newcomb , P A , Gallinger , S , Conti , D , Schumacher , F , Casey , G , Taipale , J , Aaltonen , L A , Cheadle , J P , Dunlop , M G , Tomlinson , I P & Houlston , R S 2016 , ' Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer ' , British Journal of Cancer , vol. 115 , no. 2 , pp. 266-272 . https://doi.org/10.1038/bjc.2016.188

Title: Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
Author: Jarvis, David; Mitchell, Jonathan S.; Law, Philip J.; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Bohm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Farrington, Susan M.; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Timothy S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Win, Aung K.; Hopper, John L.; Jenkins, Mark A.; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Aaltonen, Lauri A.; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Houlston, Richard S.
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Heikki Järvinen / Principal Investigator
University of Helsinki, Clinicum
University of Helsinki, II kirurgian klinikka
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
Date: 2016-07-12
Language: eng
Number of pages: 7
Belongs to series: British Journal of Cancer
ISSN: 0007-0920
URI: http://hdl.handle.net/10138/167038
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 x 10(-4)) and 1.40 (95% CI: 1.14-1.72, P = 1.2 x 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.
Subject: Mendelian randomisation
adiposity
colorectal cancer
BODY-MASS INDEX
OBESITY
METAANALYSIS
EPIDEMIOLOGY
INSTRUMENTS
WEIGHT
COMMON
3122 Cancers
3121 General medicine, internal medicine and other clinical medicine
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