Long-term aspirin use significantly lowered the risk of developing colorectal cancer (CRC) in Lynch syndrome carriers while ameliorating the added risk associated with obesity. These conclusions come from a new analysis from the CAPP2 trial published in the Journal of Clinical Oncology.1
Further, the U.S. Preventive Services Task Force (USPSTF) issued a draft guideline today that would recommend the use of low-dose aspirin for the prevention of cardiovascular disease and CRC in certain individuals deemed to be at greater risk.2 If it becomes a final recommendation statement, the USPSTF would be reversing their previous decision against the use of aspirin for CRC prevention.
In obese Lynch syndrome carriers, the risk of developing CRC was 134 percent higher compared with a reference group of normal and underweight participants. In the placebo arm, the risk of developing CRC increased by 175 percent when body mass index (BMI) was greater than 30 kg/m2. However, in the aspirin arm, the increase CRC risk associated with obesity was not statistically significant.
“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," says co-author John Burn, professor of Clinical Genetics at Newcastle University, who led the international research collaboration. “But, if there is a strong family history of cancer, then people may want to weigh up the cost-benefits particularly as these days drugs which block acid production in the stomach are available over the counter."
In the CAPP2 trial, Lynch syndrome carriers were randomized to aspirin at 600 mg per day or an aspirin placebo. Within these groups, patients also received resistant starch at 30 grams per day or a starch placebo. Individuals in the study had a history of a cured Lynch syndrome-related neoplasm and had an intact colon. The primary endpoint of the study was the development of CRC.
The mean duration of treatment was 25 months and the mean follow-up was 55.7 months. BMI was recorded according to WHO criteria, which defines underweight at less than 18.5, normal weight as 18.5 to 24.99, overweight as 25 to 29.99, and obese as ≥30 kg/m2. In the analysis, those who were underweight (14 patients) were combined with normal weight individuals (418 patients) to create a reference group.
Among those with evaluable BMI (719 patients), 117 developed colorectal adenoma during the treatment phase of the trial. After adjusting for age, sex, aspirin use, and other factors, there was a nonsignificant increase in the risk of developing a colorectal adenoma in obese individuals compared with the reference group. This trend was observed across those with MLH1 and MSH2 mutations.
Across all individuals enrolled in the CAPP2 study, 55 developed CRC, with a trend toward a higher incidence in overweight individuals. When BMI was measured as a continuous variable, each 1 kg/m2 gained increased the risk of developing CRC by 7 percent.
For those with the MLH1 gene mutation, the risk of developing CRC was significantly higher in obese individuals. In individuals with the MSH2 mutation, obesity was not found to significantly impact the risk of developing CRC.