Losing weight and taking aspirin protect people who are genetically predisposed to colorectal cancer from developing the disease, according to a randomized study of 937 Lynch syndrome patients published online Aug. 17 in the Journal of Clinical Oncology.
In the general population, obesity is a known risk factor for colorectal cancer (CRC), especially in men, and aspirin has been shown to have protective benefits. The investigators wondered if that also held true in Lynch syndrome (LS), the most common cause of hereditary bowel cancer (J Clin Oncol. 2015 Aug 17. doi. 10.1200/JCO.2014.58.9952).
This “study showed some evidence that the excess CRC risk in patients with LS is abrogated by regular aspirin consumption. … Such patients are likely to benefit from obesity prevention and/or regular aspirin,” wrote Mohammad Movahedi, Ph.D., of Beheshti University of Medical Sciences in Tehran, Iran, and associates.
In a 2 × 2 factorial design, the LS subjects were randomly assigned to aspirin 600 mg/day or placebo, plus resistant starch 30 g/day or placebo, for a mean of about 2 years. Resistant starch is a dietary fiber.
After a mean follow-up of 4.6 years, CRC was diagnosed in 55 (6%) subjects. The risk of disease was 2.41 times greater for LS patients with a body mass index (BMI) of 25 kg/m2 or higher than for subjects below that mark (95% confidence interval, 1.22-4.85). Each 1-kg/m2 increase in BMI was associated with a 7% increase in CRC risk, about twice the excess risk obesity causes in the general population.
Obesity increased the risk of CRC only in LS subjects who did not get aspirin (adjusted hazard ratio, 2.75; 95% CI, 1.12-6.79; P = .03).
The obesity-CRC link was statistically significant only in men. Increasing BMI also seemed to pose a greater threat to men than to women, but the difference was not significant, Dr. Movahedi and associates said.
LS is the result of several mutations in DNA repair genes, but only one seemed to matter in the trial: Obesity was associated with a 3.72-fold greater risk for CRC in LS patients with the MLH1 mutation but did not increase risk in those with MSH2 or MSH6 mutations.
Obesity sets patients up for chronic inflammation, which is thought to contribute to cancer risk. That dynamic might be amplified in LS patients with stem cells that accumulate DNA damage because of a faulty repair system, the investigators said. Aspirin’s anti-inflammatory properties might counter the effect.
The “observation of sex-dependent greater CRC risk among obese men in the general population accords with our current findings in patients with LS and with reports from other observational studies,” they noted.
There were slightly more women in the trial than men, and the mean age in the study was 45.2 years.
Dr. Movahedi had no disclosures. The work was funded by the British Medical Research Council, Cancer Research UK, and the European Union, among others.
The new AGA guideline on Lynch syndrome was published in the September issue of Gastroenterology (2015 Jul 28 [doi: 10.1053/j.gastro.2015.07.036]) and summarized in the September issue of GI & Hepatology News.