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

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 adip...

Descripción completa

Detalles Bibliográficos
Autores principales: Jarvis, David, Mitchell, Jonathan S, Law, Philip J, Palin, Kimmo, Tuupanen, Sari, Gylfe, Alexandra, Hänninen, 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, Böhm, Jan, Meklin, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947703/
https://www.ncbi.nlm.nih.gov/pubmed/27336604
http://dx.doi.org/10.1038/bjc.2016.188
_version_ 1782443212406784000
author Jarvis, David
Mitchell, Jonathan S
Law, Philip J
Palin, Kimmo
Tuupanen, Sari
Gylfe, Alexandra
Hänninen, 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
Böhm, Jan
Meklin, 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
author_facet Jarvis, David
Mitchell, Jonathan S
Law, Philip J
Palin, Kimmo
Tuupanen, Sari
Gylfe, Alexandra
Hänninen, 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
Böhm, Jan
Meklin, 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
author_sort Jarvis, David
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4947703
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-49477032016-07-27 Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer Jarvis, David Mitchell, Jonathan S Law, Philip J Palin, Kimmo Tuupanen, Sari Gylfe, Alexandra Hänninen, 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 Böhm, Jan Meklin, 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 Br J Cancer Genetics and Genomics 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. Nature Publishing Group 2016-07-12 2016-06-23 /pmc/articles/PMC4947703/ /pubmed/27336604 http://dx.doi.org/10.1038/bjc.2016.188 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Genetics and Genomics
Jarvis, David
Mitchell, Jonathan S
Law, Philip J
Palin, Kimmo
Tuupanen, Sari
Gylfe, Alexandra
Hänninen, 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
Böhm, Jan
Meklin, 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
Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title_full Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title_fullStr Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title_full_unstemmed Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title_short Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
title_sort mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947703/
https://www.ncbi.nlm.nih.gov/pubmed/27336604
http://dx.doi.org/10.1038/bjc.2016.188
work_keys_str_mv AT jarvisdavid mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT mitchelljonathans mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT lawphilipj mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT palinkimmo mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT tuupanensari mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT gylfealexandra mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT hanninenulrikaa mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT cajusotatiana mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT tanskanentomas mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kondelinjohanna mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kaasineneevi mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT sarinanttipekka mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kapriojaakko mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT erikssonjohang mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT rissanenharri mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT knektpaul mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT pukkalaeero mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT jousilahtipekka mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT salomaaveikko mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT ripattisamuli mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT palotieaarno mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT jarvinenheikki mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT renkonensinisalolaura mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT lepistoanna mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT bohmjan mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT meklinjukkapekka mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT altassannadaa mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT pallesclaire mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT martinlynn mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT barclayella mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT farringtonsusanm mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT timofeevamarian mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT meyerbrianf mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT wakilsalmam mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT campbellharry mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT smithchristopherg mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT idziaszczykshelley mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT maughantimothys mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kaplanrichard mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kerrrachel mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT kerrdavid mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT buchanandanield mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT winaungk mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT hopperjohnl mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT jenkinsmarka mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT lindornoralanem mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT newcombpollya mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT gallingersteve mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT contidavid mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT schumacherfred mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT caseygraham mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT taipalejussi mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT aaltonenlauria mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT cheadlejeremyp mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT dunlopmalcolmg mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT tomlinsonianp mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer
AT houlstonrichards mendelianrandomisationanalysisstronglyimplicatesadipositywithriskofdevelopingcolorectalcancer