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

Autor: Daniel D. Buchanan, Jussi Taipale, Lynn Martin, Tim Maughan, Susan M. Farrington, Ella Barclay, Rachel Kerr, David V. Conti, Aung Ko Win, Jeremy Peter Cheadle, Tomas Tanskanen, Shelley Idziaszczyk, Aarno Palotie, Kimmo Palin, Christopher Smith, Samuli Ripatti, Harri Rissanen, Heikki Järvinen, Mark A. Jenkins, David Jarvis, Brian F. Meyer, Jonathan S. Mitchell, Salma M. Wakil, Jaakko Kaprio, Ian Tomlinson, Noralane M. Lindor, Alexandra E. Gylfe, Laura Renkonen-Sinisalo, Eero Pukkala, Eevi Kaasinen, Richard S. Houlston, Claire Palles, Nada Al-Tassan, Richard Kaplan, Anna Lepistö, David J. Kerr, Polly A. Newcomb, Sari Tuupanen, Fred Schumacher, Antti-Pekka Sarin, Veikko Salomaa, Malcolm G. Dunlop, Lauri A. Aaltonen, Graham Casey, Johan G. Eriksson, S. Gallinger, Ulrika A. Hänninen, Pekka Jousilahti, Harry Campbell, Jan Böhm, Tatiana Cajuso, Philip J. Law, Paul Knekt, Maria Timofeeva, John L. Hopper, Johanna Kondelin, Jukka Pekka Meklin
Přispěvatelé: School of Medicine / Clinical Medicine, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Medicum, Department of Medical and Clinical Genetics, Institute for Molecular Medicine Finland, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Samuli Olli Ripatti / Principal Investigator, Aarno Palotie / Principal Investigator, Heikki Järvinen / Principal Investigator, Department of Surgery, II kirurgian klinikka, Jussi Taipale / Principal Investigator, Biostatistics Helsinki, Complex Disease Genetics, Genomics of Neurological and Neuropsychiatric Disorders, Genetic Epidemiology
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Colorectal cancer
3122 Cancers
Genome-wide association study
colorectal cancer
Polymorphism
Single Nucleotide
03 medical and health sciences
symbols.namesake
Prostate cancer
Random Allocation
0302 clinical medicine
Breast cancer
Internal medicine
medicine
EPIDEMIOLOGY
Humans
Mendelian randomisation
COMMON
METAANALYSIS
2. Zero hunger
adiposity
business.industry
Cancer
Genetics and Genomics
INSTRUMENTS
Middle Aged
medicine.disease
3. Good health
BODY-MASS INDEX
030104 developmental biology
OBESITY
3121 General medicine
internal medicine and other clinical medicine
030220 oncology & carcinogenesis
Immunology
Mendelian inheritance
symbols
Female
WEIGHT
Skin cancer
business
Colorectal Neoplasms
Body mass index
Genome-Wide Association Study
Zdroj: British Journal of Cancer
Jarvis, D, Mitchell, J S, Law, P J, Palin, K, Tuupanen, S, Gylfe, A, Hänninen, 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, Böhm, J, Meklin, 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 . https://doi.org/10.1038/bjc.2016.188
ISSN: 1532-1827
0007-0920
Popis: Article
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.
published version
peerReviewed
Databáze: OpenAIRE
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