Researchers involved in the international multi-institutional study, CAPP2, have reported that the use of daily aspirin may reduce the incidence of colorectal adenomas and cancers in individuals with hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. The details of this study were presented on September 21, 2009 at Europe’s largest cancer congress, ECCO 15-ESMO 34, in Berlin.[1]

HNPCC results from inherited mutations in genes involved in DNA mismatch repair. These mutations greatly increase the risk of developing colorectal cancer. In individuals with an HNPCC mutation, the average age at diagnosis of colorectal cancer is 44 years, compared with 64 years in the general population. Overall, roughly 3% to 5% of all colorectal cancers are thought to result from HNPCC mutations. Other cancers that are more common in HNPCC families include cancers of the endometrium, ovary, small intestine, ureter, and renal pelvis. 

In previous studies the regular use of aspirin or non-steroidal anti-inflammatory drugs has been shown to reduce the risk of colon polyps and colorectal cancer in high-risk patients. Resistant starch is starch that travels through the small intestine without being digested. (Resistant starch is found in many foods, including seeds, legumes, unprocessed whole grains, unripe fruit, and more.) As a result, resistant starch is sometimes classified as a type of dietary fiber. Researchers have speculated that it may provide similar benefits to fiber in preventing colorectal adenomas and cancers.

The CAPP2 study was a randomized, placebo-controlled, multicenter, international clinical trial that evaluated the effects of aspirin and/or resistant starch on the subsequent development of colorectal cancer among HNPCC carriers. The initial results of this study were published in the December 11, 2008 issue of the New England Journal of Medicine. At that time the study involved 746 patients at 43 centers who were randomized to receive one of four regimens: aspirin plus placebo, aspirin plus resistant starch, resistant starch plus placebo, and placebo plus placebo. The resistant starch was given in the form of Novelose at 30g per day, and the aspirin was given at a dose of 600 mg per day. The initial evaluation of this study, with a median follow-up of 29 months, showed that the use of aspirin and/or resistant starch for four years had no effect on the incidence of colon cancer among individuals with Lynch Syndrome.

The CAPP2 trial now includes 1,071 individuals with the HNPCC mutation. At ECCO -14 ESMO 34 researchers presented long-term data on 628 patients. There were 240 adenomas detected in 218 of these 628 patients. They reported six colon cancers in the aspirin group and 16 in the placebo group. There were 18 HNPCC-related cancers in the aspirin group and 31 in the control group (P<0.02). They also reported, “The protective effect appears to persist for at least 6 years after the episode of aspirin use and correlates with the duration of aspirin use on trial.” Patients in this study received aspirin for four years. There were fewer strokes and heart attacks in the aspirin group. Eleven patients in the aspirin group experienced side effects, including gastrointestinal bleeds or ulcers, compared with nine patients in the placebo group.

The researchers concluded that long-term aspirin use provides benefit to individuals with HNPCC mutations. Future research will be directed toward evaluating the effects of a lower dose of aspirin.

Comments: These findings are convincing that long-term aspirin use can decrease the risk of colorectal neoplasms and possibly other HNPCC-related cancers.

Reference:

[1] Burn J, Gerdes AM, Mecklin JP, et al. Aspirin prevents cancer in Lynch syndrome. European Journal of Cancer Supplements, Vol. 7, No. 3, September 2009. Abstract O-6000.