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Low-Dose Aspirin Cuts Colon Cancer Risk

Posted: Wednesday, November 03, 2010

The use of long-term low-dose aspirin reduced both the incidence and the mortality associated with colorectal cancer, a 20-year follow-up of randomized trials showed.

Aspirin use for a scheduled mean duration of six years cut the incidence of colon cancer by about one-quarter (HR 0.76, 95% CI 0.60 to 0.96, P=0.02) over a median of 18.3 years of follow-up, according to a new study.

Moreover, the risk of death from the disease fell by a third (HR 0.65, 95% CI 0.48 to 0.88, P=0.005), the researchers reported online in The Lancet. Unlike colon cancer, aspirin use was not associated with a reduction in incidence of rectal cancer (HR 0.90, 95% CI 0.63 to 1.30, P=0.58) or mortality (HR 0.80, 95% CI 0.50 to 1.28, P=0.35). However, the researchers wrote, "benefit increased with scheduled duration of treatment. The risk of proximal colon cancer was reduced by about 70% ... and also reduced the risk of rectal cancer. They had previously shown that five years of high-dose aspirin use was associated with a 30% reduction in the incidence of colorectal cancer over 20 years.

But high doses can have adverse bleeding consequences when taken for long periods, and the effects of lower doses on colorectal cancer risk had not been established. So the researchers looked at data from five trials conducted in the U.K. and Sweden that included a total of 16,488 participants. The trials were designed to assess the effects of aspirin in primary or secondary prevention of vascular events.

Two of the trials randomized patients to 75 mg aspirin or placebo daily, a third compared 300 mg or 1,200 mg daily with placebo, and another compared 500 mg daily with no aspirin. The other trial randomized patients to 30 mg or 283 mg of aspirin daily. The researchers confined their data analysis to the four trials that compared aspirin with a control.

Among the 14,033 patients in those trials, there were 391 cases of colorectal cancer and 240 deaths during a median follow-up of 18.3 years. Analysis of subsite data determined that the reduction in colon cancer incidence was limited to the proximal colon:

* Proximal colon, HR 0.45 (95% CI 0.28 to 0.74, P=0.001)
* Distal colon, HR 1.10 (95% CI 0.73 to 1.64, P=0.66)

Similar risk reductions were seen for mortality:

* Proximal colon, HR 0.34 (95% CI 0.18 to 0.66, P=0.001)
* Distal colon, HR 1.21 (95% CI 0.66 to 2.24, P=0.54)

Case fatality rates also were higher for proximal cases (RR 1.37, 95% CI 1.02 to 1.84, P=0.04).

Differences between proximal and distal colon cancers also have been seen for other treatments, the researchers noted.

"There are many differences in normal physiology between the proximal and distal colon, due partly to their different embryological origins, and in risk factors for cancers in the two sites, in mechanisms of carcinogenesis, and in the molecular and genetic characteristics of the cancers," they explained.

The study had several other important findings, according to the authors. It showed that 75 mg of aspirin daily was as effective in preventing disease as higher doses, and that the decrease in mortality was "statistically robust and clinically important." They also pointed out that their seven- to eight-year estimate of the latent period before a mortality effect was seen could have been too long.

The study did have limitations. For instance, the researchers noted that their findings were not generalizable to other regimens, such as alternate-day aspirin use.

In addition, patients on aspirin might have had more diagnostic evaluations for problems such as gastrointestinal bleeding that could have led to earlier diagnosis of cancer compared with patients receiving placebo, although in none of the trials was there any evidence of this.

The finding that fewer deaths occurred among the aspirin groups without any evidence of earlier diagnosis suggests that there may be a difference in tumor aggressiveness in patients receiving aspirin compared with nonusers, according to the researchers.

"The suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancers by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important," they wrote.
Practice Pearls:

* Explain to interested patients that low-dose aspirin use decreased the incidence of colon cancer by about one-quarter and mortality by about a third over a median follow-up of nearly 20 years.

* Note that further analysis determined that the reduction in colon cancer incidence was limited to the proximal colon.

Source: http://www.diabetesincontrol.com/index.php?option=com_content&view=article&id=10002&catid=1&Itemid=17, Rothwell P, et al "Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials" The Lancet 2010; DOI: 10.1016/S0140-6736(10)61543-7.