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Aspirin reduces increased CRC risk associated with obesity, Lynch syndrome
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An increased risk for colorectal cancer was found to be associated with obesity in patients with Lynch syndrome, but regularly taking aspirin reversed the risk, according to study results.
“This is important for people with Lynch syndrome but affects the rest of us too. Lots of people struggle with their weight and this suggests the extra cancer risk can be cancelled by taking an aspirin,” Sir John Burn, MD, professor of clinical genetics at Newcastle University in the UK, said in a press release. “This research adds to the growing body of evidence which links an increased inflammatory process to an increased risk of cancer. Obesity increases the inflammatory response. One explanation for our findings is that the aspirin may be suppressing that inflammation, which opens up new avenues of research into the cause of cancer.”
Aiming to explore the association between cancer risk and overweight or obesity in patients with Lynch syndrome, Burn and colleagues prospectively studied 937 Lynch syndrome carriers (mean age at enrollment, 44.9 years) who were enrolled in a multicenter randomized controlled trial of aspirin and/or resistant starch interventions from January 1999 to March 2005 (CAPP2 study).
Using a 2 x 2 factorial design, patients were randomly assigned to receive 600 mg aspirin per day and/or 30 g resistant starch per day or placebo for a mean of 25 months (median, 24.4 months). Height and weight data was collected at enrollment and WHO criteria were used to determine BMI (34% overweight, 15% obese). The earliest enrolled patients reached 10 years of follow up at the time of Burn and colleagues’ analysis (mean follow up, 55.7 months; median, 53.1 months).
Overall, 55 participants developed colorectal cancer, and the risk was higher for obese patients compared with those who were underweight or normal weight (adjusted HR = 2.34; 95% CI, 1.17-4.67). Increased risk for colorectal cancer was especially increased in obese participants with MLH1 mutation (adjusted HR = 3.72; 95% CI, 1.41-9.81). Obese participants also had an increased risk for all cancers associated with Lynch syndrome (adjusted HR = 1.81; 95% CI, 1.08-3.03).
“For those with Lynch Syndrome, we found that every unit of BMI above what is considered healthy increased the risk of bowel cancer by 7%,” John Mathers, PhD, professor of human nutrition at Newcastle University, said in the press release. “What is surprising is that even in people with a genetic predisposition for cancer, obesity is also a driver of the disease. Indeed, the obesity-associated risk was twice as great for people with Lynch Syndrome as for the general population. The lesson for all of us is that everyone should try to maintain a healthy weight and for those already obese the best thing is to lose weight. However, for many patients this can be very difficult so a simple aspirin may be able to help this group.”
The placebo group showed a significant association between increased BMI and colorectal cancer risk (aHR = 1.1; 95% CI, 1.03-1.17), while there was no increased risk for those assigned to receive aspirin (aHR = 1; 95% CI, 0.9-1.12). For obese participants in the placebo group, adjusted HR for colorectal cancer was 2.75 (95% CI, 1.12-6.75) compared with 2 (95% CI; 0.61-6.7) in the aspirin group.
“Our study suggests that the daily aspirin dose of 600 mg per day removed the majority of the increased risk associated with higher BMI,” Tim Bishop, PhD, from the University of Leeds, said in the press release. “However, this needs to be shown in a further study to confirm the extent of the protective power of the aspirin with respect to BMI.”
“We may be seeing a mechanism in humans whereby aspirin is encouraging genetically damaged stem cells to undergo programmed cell death,” Burn said. “This would have an impact on cancer.” – by Adam Leitenberger
Disclosure: Burn reports employment, leadership and stock/other ownership ties to QuantuMDx, honoraria and research funding from Bayer, consulting or advisory role with AstraZeneca. Bishop and Mathers report no relevant financial disclosures. Please see the study for a full list of all other researchers’ relevant financial disclosures.
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