Aspirin Associated with Lower Incidence of Colon Cancer in Patients with Lynch Syndrome

In a press conference at the ECCO 15-ESMO 34 Joint Congress, John Burn, MD, Institute of Human Genetics, Newcastle University, United Kingdom, discussed follow-up results to a trial he and his colleagues conducted that investigated the effectiveness of ordinary aspirin in preventing colon cancer. Dr Burn noted that “Aspirin has been associated with cancer chemoprevention since the late 1980s,” when researchers observed that people who took aspirin regularly for chronic conditions like arthritis had a lower incidence of certain cancers. Since then, various studies have demonstrated a correlation between frequent use of NSAIDS and reduced risk of colon cancer.

The trial by Dr Burn and colleagues included 1071 carriers of an inherited genetic mutation that causes Lynch syndrome, a malignancy that develops in the digestive tract. It most commonly arises in the colorectal region, and it is also known as hereditary nonpolyposis colorectal cancer. In addition to colorectal cancer, people with Lynch syndrome are at greater risk for many other solid tumors. Women who carry the Lynch syndrome mutation are prone to endometrial and ovarian cancers.

Patients were recruited from 42 centers in 16 countries and randomized to receive either 600 mg of aspirin per day or 30 g of Novelose, a resistant starch. Patients stayed on the regimen for a median of 29 months, and preliminary results published in a December issue of New England Journal of Medicine were disappointing, said Dr Burn. Researchers observed no evidence that aspirin helped reduce the incidence of colon cancer in this genetically predisposed population.

Several years after the study concluded, Dr Burn and his associates decided to track down the patients who participated. They were able to locate approximately 75% of the patients and found something surprising: at 4 years after randomization, the benefits of daily aspirin use became apparent. Dr Burn said, to date, there have been 6 cases of colon cancer in the aspirin group compared with 16 in the placebo group, a statistically significant result. For patients enrolled in the study for 2 years, 6 developed multiple cancers; of these, 5 were in the placebo group. The rate of endometrial cancer was also lower in women who took aspirin.

The benefits of aspirin regarding chemoprevention persisted for at least 6 years after discontinuation; those who remained on aspirin longer were less likely to develop cancer. In the original cohort of 1000 patients, 11 patients in the aspirin group developed significant gastrointestinal bleeding compared with 9 in the placebo group. “In terms of the overall side effects profile,” Dr Burn said, “the differences were not that great,” but he noted that the incidence of cardiovascular events was reduced in the aspirin group.

Although researchers are uncertain how aspirin protects against cancer, Dr Burn said he believes it has an effect on cancer stem cells, targeting the cancer even before it has been detected. The investigators would like to expand their study, enrolling a larger number of patients with Lynch syndrome and evaluating different doses.

Dr Burn noted that “approximately 3% to 5% of colon and endometrial cancers are attributable to [the Lynch] gene defect,” yet 1 in 6 colon cancers have a breakdown in this gene system. “One might reasonably extrapolate that if [aspirin] is preventing cancers in the hereditary defect, it might be suppressing sporadic forms, also.”

ECCO/ESMO Abstract O-6000