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

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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)	266-272
Number of pages	7
Journal	British Journal of Cancer
Volume	115
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2016.188
State	Published - 12 Jul 2016
Externally published	Yes

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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), 266-272. https://doi.org/10.1038/bjc.2016.188

@article{e03e94f029be4698bf37d811b5aa5853,

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.",

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 Sarin, {Antti Pekka} 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 Meklin, {Jukka Pekka} 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,

day = "12",

doi = "10.1038/bjc.2016.188",

language = "English",

volume = "115",

pages = "266--272",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "2",

}

Jarvis, D, Mitchell, JS, Law, PJ, Palin, K, Tuupanen, S, Gylfe, A, Hänninen, UA, Cajuso, T, Tanskanen, T, Kondelin, J, Kaasinen, E, Sarin, AP, 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, JP, 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. 266-272. 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.

UR - http://www.scopus.com/inward/record.url?scp=84976273894&partnerID=8YFLogxK

U2 - 10.1038/bjc.2016.188

DO - 10.1038/bjc.2016.188

M3 - Article

C2 - 27336604

AN - SCOPUS:84976273894

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

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