Aspirin Reduces Obesity-Related Colorectal Cancer Risk in Patients With Lynch Syndrome
In an analysis of a randomized trial of aspirin in patients with Lynch syndrome reported in the Journal of Clinical Oncology, Movahedi et al found that obesity was associated with an increased risk of colorectal cancer, with the excess risk being restricted to those not receiving aspirin.
Study Details
In the CAPP2 trial, patients with Lynch syndrome were randomly assigned to receive aspirin 600 mg/d or placebo (plus resistant starch 30 g/d or placebo in a 2×2 factorial design). The mean intervention period was 25.0 months, and the mean follow-up was 55.7 months.
Colorectal Cancer Risk
Overall, 55 of 937 patients developed colorectal cancer. Colorectal cancer risk was significantly higher in obese vs underweight or normal-weight patients (hazard ratio [HR] = 2.34, P = .02), with the risk increasing by 7% for each 1-kg/m2 increase in body mass index. The risk of all Lynch syndrome–related cancers was also significantly higher in obese patients (HR = 1.81, P = .03).
Obesity was associated with an increased risk of colorectal cancer in patients with MLH1 mutation (HR = 3.72, P = .05) but not in those with MSH2 or MSH6 mutation. The obesity-related excess colorectal cancer risk was restricted to patients who received placebo vs aspirin (adjusted HR = 2.75, P = .03).
The investigators concluded: “Obesity is associated with substantially increased [colorectal cancer] risk in patients with [Lynch syndrome], but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.”
John C. Mathers, PhD, of Newcastle University, is the corresponding author of the Journal of Clinical Oncology article.
The CAPP2 study was supported by the Medical Research Council, Cancer Research UK, European Union, Cancer Council Victoria, Technology and Human Resources for Industry Programme–South Africa, Sigrid Juselius Foundation, and Finnish Cancer Foundation.
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