Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: A prospective investigation in the CAPP2 study

Mohammad Movahedi, D. Timothy Bishop, Finlay Macrae, Jukka Pekka Mecklin, Gabriela Moeslein, Sylviane Olschwang, Diana Eccles, D. Gareth Evans, Eamonn R. Maher, Lucio Bertario, Marie Luise Bisgaard, Malcolm G. Dunlop, Judy W.C. Ho, Shirley V. Hodgson, Annika Lindblom, Jan Lubinski, Patrick J. Morrison, Victoria Murday, Raj S. Ramesar, Lucy SideRodney J. Scott, Huw J.W. Thomas, Hans F. Vasen, John Burn, John C. Mathers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS). Patients and Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2×2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months. Results: During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41 X (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03). Conclusion: Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.

Original languageEnglish
Pages (from-to)3591-3597
Number of pages7
JournalJournal of clinical oncology
Issue number31
Publication statusPublished - 1 Nov 2015


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