Journal article
Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
David Jarvis, Jonathan S Mitchell, Philip J Law, Kimmo Palin, Sari Tuupanen, Alexandra Gylfe, Ulrika A Hanninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti-Pekka Sarin, Jaakko Kaprio, Johan G Eriksson, Harri Rissanen, Paul Knekt, Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti Show all
BRITISH JOURNAL OF CANCER | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/bjc.2016.188
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..
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Grants
Awarded by Cancer Research UK (Bobby Moore Fund for Cancer Research UK)
Awarded by Programme Grant funding from Cancer Research UK
Awarded by European Union
Awarded by COST Action in the UK
Awarded by Academy of Finland (Finnish Center of Excellence Program)
Awarded by European Research Council (ERC)
Awarded by Nordic Center of Excellence - NordForsk
Awarded by State Research Funding of Kuopio University Hospital
Awarded by Academy of Finland
Awarded by Finnish Academy
Awarded by National Institute of Alcohol Abuse and Alcoholism
Awarded by ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4
Awarded by National Cancer Institute
Awarded by CCFR centre: Australasian Colorectal Cancer Family Registry
Awarded by CCFR centre: USC Consortium Colorectal Cancer Family Registry
Awarded by CCFR centre: Mayo Clinic Cooperative Familial Registry for Colon Cancer Studies
Awarded by CCFR centre: Ontario Familial Colorectal Cancer Registry
Awarded by CCFR centre: Seattle Colorectal Cancer Family Registry
Awarded by CCFR centre: University of Hawaii Colorectal Cancer Family Registry
Awarded by National Cancer Institute, National Institutes of Health
Awarded by Cancer Surveillance System of the Fred Hutchinson Cancer Research Center-Control
Awarded by Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute
Awarded by National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER)
Awarded by National Cancer Institute's Surveillance, Epidemiology and End Results Program
Awarded by Centers for Disease Control and Prevention's National Program of Cancer Registries
Awarded by Cancer Research UK
Awarded by Medical Research Council
Awarded by Tenovus Cancer Care
Awarded by MRC
Awarded by Academy of Finland (AKA)
Funding Acknowledgements
[ "We are grateful to all individuals who participated in the various studies. This study made use of genotyping data from the 1958 Birth Cohort, kindly made available by the Wellcome Trust Case Control Consortium 2. A full list of the investigators who contributed to the generation of the data is available at http://www.wtccc.org.uk/. At the Institute of Cancer Research, this work was supported by Cancer Research UK (C1298/A8362-Bobby Moore Fund for Cancer Research UK). Additional support was provided by the National Cancer Research Network. DJ was supported by a summer student grant from the BBRSC. In Edinburgh, the work was supported by Programme Grant funding from Cancer Research UK (C348/A12076). In Oxford, additional funding was provided by the Oxford Comprehensive Biomedical Research Centre and the EU FP7 CHIBCHA grant. Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford was provided by grant (090532/Z/09/Z). We are grateful to many colleagues within UK Clinical Genetics Departments (for CORGI) and to many collaborators who participated in the VICTOR and QUASAR2 trials. We also thank colleagues from the UK National Cancer Research Network (for NSCCG). Support from the European Union (FP7/207-2013, grant 258236) and FP7 collaborative project SYSCOL and COST Action in the UK is also acknowledged (BM1206). The COIN and COIN-B trials were funded by Cancer Research UK and the Medical Research Council and were conducted with the support of the National Institute of Health Research Cancer Research Network. COIN and COIN-B translational studies were supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit (2011-2014). NAA, RPM and SMW were funded and supported by KFSHRC. In Finland, this work was supported by grants from the Academy of Finland (Finnish Center of Excellence Program 2012-2017, 250345), the Jane and Aatos Erkko Foundation, the Finnish Cancer Society (to KP), the European Research Council (ERC; 268648), the Sigrid Juselius Foundation, SYSCOL, the Nordic Information for Action eScience Center (NIASC), the Nordic Center of Excellence financed by NordForsk (project 62721, to KP) and State Research Funding of Kuopio University Hospital (B1401). We acknowledge the computational resources provided by the ELIXIR node, hosted at the CSC-IT Center for Science, Finland, and funded by the Academy of Finland (grants 271642 and 263164), the Ministry of Education and Culture, Finland. VS was supported by the Finnish Academy (grant number 139635). Sample collection and genotyping in the Finnish Twin Cohort has been supported by the Wellcome Trust Sanger Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 (201413), the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502 and AA-00145 to Richard J Rose, and K02AA018755 to Danielle M Dick) and the Academy of Finland (100499, 205585, 265240 and 263278 to Jaakko Ka.prio (JK)).", "The work of the Colon Cancer Family Registry (CCFR) was supported by the National Cancer Institute (UM1 CA167551), National Institutes of Health and through cooperative agreements with the following CCFR centres: Australasian Colorectal Cancer Family Registry (U01 CA074778, U01/U24 CA097735), USC Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), Mayo Clinic Cooperative Familial Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794) and University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). The CCFR Illumina GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (U01 CA122839 and R01 CA143237 to GC). Seattle CCFR research was also supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center-Control Nos. N01-CN-67009 (1996-2003), N01-PC-35142 (2003-2010) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (Contract No. HHSN2612013000121, 2010-2017) with additional support from the Fred Hutchinson Cancer Research Center. The collection of cancer incidence data for the State of Hawaii used in this study was supported by the Hawaii Department of Health as part of the statewide cancer reporting program mandated by Hawai`i Revised Statutes; the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) awarded to the University of Hawaii (Control Nos. N01-PC-67001 1996-2003, N01-PC-35137 2003-10, Contract Nos. HHSN26120100037C 2010-13, HHSN261201300009I 2010-). The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program contract HHSN261201000035C-awarded to the University of Southern California, and contract HHSN261201000034C-awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement-U58DP003862-01-awarded to the California Department of Public Health." ]