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J Clin Oncol. 2015 Nov 1;33(31):3591-7. doi: 10.1200/JCO.2014.58.9952. Epub 2015 Aug 17.

Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study.

Author information

1
Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands.
2
Mohammad Movahedi, Beheshti University of Medical Sciences, Tehran, Iran; Mohammad Movahedi and D. Timothy Bishop, University of Leeds, Leeds; Diana Eccles, University of Southampton, Southampton; D. Gareth Evans, St Mary's Hospital, Manchester; Eamonn R. Maher, University of Birmingham, Birmingham; Malcolm G. Dunlop, Western General Hospital, Edinburgh; Shirley V. Hodgson, St George's Hospital; Lucy Side, University College London; Huw J.W. Thomas, St Mark's Hospital, Imperial College, London; Patrick J. Morrison, Queens University Belfast, Belfast City Hospital Health and Social Care Trust, Belfast; Victoria Murday, Yorkhill Hospital, Glasgow; John Burn and John C. Mathers, Newcastle University, Newcastle upon Tyne, United Kingdom; Finlay Macrae, Royal Melbourne Hospital, Melbourne, Victoria; Rodney J. Scott, John Hunter Hospital, New Lambton, New South Wales, Australia; Jukka-Pekka Mecklin, Jyväskylä Central Hospital, Jyväskylä, Finland; Gabriela Moeslein, HELIOS St Josefs Hospital, Bochum-Linden, Germany; Sylviane Olschwang, Institut Paoli Calmettes, Marseille, France; Lucio Bertario, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Marie-Luise Bisgaard, University of Copenhagen, Hvidovre, Denmark; Judy W.C. Ho, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China; Annika Lindblom, Karolinska Institutet, Stockholm, Sweden; Jan Lubinski, International Hereditary Cancer Centre, Szczecin, Poland; Raj S. Ramesar, University of Cape Town, South Africa; and Hans F. Vasen, Netherlands Foundation of the Detection of Hereditary Tumours and Leiden University, Leiden, the Netherlands. john.mathers@ncl.ac.uk.

Abstract

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× (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/m(2) 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.

PMID:
26282643
DOI:
10.1200/JCO.2014.58.9952
[Indexed for MEDLINE]

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