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 Hänninen; 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; Aarno Palotie; Heikki Järvinen; Laura Renkonen-Sinisalo; Anna Lepistö; Jan Böhm; Jukka-Pekka Meklin; Nada A Al-Tassan; Claire Palles; Lynn Martin; Ella Barclay; Susan M Farrington; Maria N Timofeeva; Brian F Meyer; Salma M Wakil; Harry Campbell; Christopher G Smith; Shelley Idziaszczyk; Timothy S Maughan; Richard Kaplan; Rachel Kerr; David Kerr; Daniel D Buchanan; Aung K Win; John L Hopper; Mark A Jenkins; Noralane M Lindor; Polly A Newcomb; Steve Gallinger; David Conti; Fred Schumacher; Graham Casey; Jussi Taipale; Lauri A Aaltonen; Jeremy P Cheadle; Malcolm G Dunlop; Ian P Tomlinson; Richard S Houlston

doi:10.1038/bjc.2016.188

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 Hänninen, 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 RipattiAarno Palotie, Heikki Järvinen, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Meklin, Nada A Al-Tassan, Claire Palles, Lynn Martin, Ella Barclay, Susan M Farrington, Maria N Timofeeva, Brian F Meyer, Salma M Wakil, Harry Campbell, Christopher G Smith, Shelley Idziaszczyk, Timothy S Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Daniel D Buchanan, Aung K Win, John L Hopper, Mark A Jenkins, Noralane M Lindor, Polly A Newcomb, Steve Gallinger, David Conti, Fred Schumacher, Graham Casey, Jussi Taipale, Lauri A Aaltonen, Jeremy P Cheadle, Malcolm G Dunlop, Ian P Tomlinson, Richard S Houlston

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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 × 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.

Original language	English
Pages (from-to)	266-72
Number of pages	7
Journal	British Journal of Cancer
Volume	115
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2016.188
Publication status	Published - 12 Jul 2016

Keywords

Adiposity
Adult
Colorectal Neoplasms
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Random Allocation
Journal Article
Meta-Analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2016.188Licence: Creative Commons: Attribution (CC BY)

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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., ... Houlston, R. S. (2016). Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer. British Journal of Cancer, 115(2), 266-72. https://doi.org/10.1038/bjc.2016.188

@article{c4e04f732ec54e24890dbf716ac597f0,

title = "Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer",

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 × 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.",

keywords = "Adiposity, Adult, Colorectal Neoplasms, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Random Allocation, Journal Article, Meta-Analysis",

author = "David Jarvis and Mitchell, {Jonathan S} and Law, {Philip J} and Kimmo Palin and Sari Tuupanen and Alexandra Gylfe and H{\"a}nninen, {Ulrika A} and Tatiana Cajuso and Tomas Tanskanen and Johanna Kondelin and Eevi Kaasinen and Antti-Pekka Sarin and Jaakko Kaprio and Eriksson, {Johan G} and Harri Rissanen and Paul Knekt and Eero Pukkala and Pekka Jousilahti and Veikko Salomaa and Samuli Ripatti and Aarno Palotie and Heikki J{\"a}rvinen and Laura Renkonen-Sinisalo and Anna Lepist{\"o} and Jan B{\"o}hm and Jukka-Pekka Meklin and Al-Tassan, {Nada A} and Claire Palles and Lynn Martin and Ella Barclay and Farrington, {Susan M} and Timofeeva, {Maria N} and Meyer, {Brian F} and Wakil, {Salma M} and Harry Campbell and Smith, {Christopher G} and Shelley Idziaszczyk and Maughan, {Timothy S} and Richard Kaplan and Rachel Kerr and David Kerr and Buchanan, {Daniel D} and Win, {Aung K} and Hopper, {John L} and Jenkins, {Mark A} and Lindor, {Noralane M} and Newcomb, {Polly A} and Steve Gallinger and David Conti and Fred Schumacher and Graham Casey and Jussi Taipale and Aaltonen, {Lauri A} and Cheadle, {Jeremy P} and Dunlop, {Malcolm G} and Tomlinson, {Ian P} and Houlston, {Richard S}",

year = "2016",

month = jul,

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doi = "10.1038/bjc.2016.188",

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volume = "115",

pages = "266--72",

journal = "British Journal of Cancer",

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publisher = "Cancer Research UK",

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Jarvis, D, Mitchell, JS, Law, PJ, Palin, K, Tuupanen, S, Gylfe, A, Hänninen, UA, Cajuso, T, Tanskanen, T, Kondelin, J, Kaasinen, E, Sarin, A-P, Kaprio, J, Eriksson, JG, 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, NA, Palles, C, Martin, L, Barclay, E, Farrington, SM, Timofeeva, MN, Meyer, BF, Wakil, SM, Campbell, H, Smith, CG, Idziaszczyk, S, Maughan, TS, Kaplan, R, Kerr, R, Kerr, D, Buchanan, DD, Win, AK, Hopper, JL, Jenkins, MA, Lindor, NM, Newcomb, PA, Gallinger, S, Conti, D, Schumacher, F, Casey, G, Taipale, J, Aaltonen, LA, Cheadle, JP, Dunlop, MG, Tomlinson, IP & Houlston, RS 2016, 'Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer', British Journal of Cancer, vol. 115, no. 2, pp. 266-72. https://doi.org/10.1038/bjc.2016.188

TY - JOUR

T1 - Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer

AU - Jarvis, David

AU - Mitchell, Jonathan S

AU - Law, Philip J

AU - Palin, Kimmo

AU - Tuupanen, Sari

AU - Gylfe, Alexandra

AU - Hänninen, Ulrika A

AU - Cajuso, Tatiana

AU - Tanskanen, Tomas

AU - Kondelin, Johanna

AU - Kaasinen, Eevi

AU - Sarin, Antti-Pekka

AU - Kaprio, Jaakko

AU - Eriksson, Johan G

AU - Rissanen, Harri

AU - Knekt, Paul

AU - Pukkala, Eero

AU - Jousilahti, Pekka

AU - Salomaa, Veikko

AU - Ripatti, Samuli

AU - Palotie, Aarno

AU - Järvinen, Heikki

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Böhm, Jan

AU - Meklin, Jukka-Pekka

AU - Al-Tassan, Nada A

AU - Palles, Claire

AU - Martin, Lynn

AU - Barclay, Ella

AU - Farrington, Susan M

AU - Timofeeva, Maria N

AU - Meyer, Brian F

AU - Wakil, Salma M

AU - Campbell, Harry

AU - Smith, Christopher G

AU - Idziaszczyk, Shelley

AU - Maughan, Timothy S

AU - Kaplan, Richard

AU - Kerr, Rachel

AU - Kerr, David

AU - Buchanan, Daniel D

AU - Win, Aung K

AU - Hopper, John L

AU - Jenkins, Mark A

AU - Lindor, Noralane M

AU - Newcomb, Polly A

AU - Gallinger, Steve

AU - Conti, David

AU - Schumacher, Fred

AU - Casey, Graham

AU - Taipale, Jussi

AU - Aaltonen, Lauri A

AU - Cheadle, Jeremy P

AU - Dunlop, Malcolm G

AU - Tomlinson, Ian P

AU - Houlston, Richard S

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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.

AB - 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.

KW - Adiposity

KW - Adult

KW - Colorectal Neoplasms

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Random Allocation

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1038/bjc.2016.188

DO - 10.1038/bjc.2016.188

M3 - Article

C2 - 27336604

SN - 0007-0920

VL - 115

SP - 266

EP - 272

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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