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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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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 |
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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 |
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