Mendelian randomisation analysis strongly implicates adiposity with risk of developing colorectal cancer.
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Date
2016-07-12Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Colorectal Neoplasms
Random Allocation
Polymorphism, Single Nucleotide
Adult
Middle Aged
Female
Male
Adiposity
Genome-Wide Association Study
Research team
Cancer Genomics
Language
eng
Date accepted
2016-05-14
License start date
2016-07
Citation
British journal of cancer, 2016, 115 (2), pp. 266 - 272
Publisher
NATURE PUBLISHING GROUP