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

Loading...
Thumbnail Image

Embargo End Date

Authors

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

Document Type

Journal Article

Date

2016-07-12

Date Accepted

2016-05-14

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.

Citation

British journal of cancer, 2016, 115 (2), pp. 266 - 272

Source Title

Publisher

NATURE PUBLISHING GROUP

ISSN

0007-0920

eISSN

1532-1827

Research Team

Cancer Genomics

Notes