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

Research output: Contribution to journalArticle

24 Scopus citations

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 languageEnglish (US)
Pages (from-to)266-272
Number of pages7
JournalBritish journal of cancer
Volume115
Issue number2
DOIs
StatePublished - Jul 12 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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