Friday, December 10, 2010

Aspirin and Colon Cancer

There have been reports in the news lately about two different articles in medical journals: (1) whether daily aspirin use reduces the incidence of colon cancer, and (2) the expense and morbidity of robotic surgery as opposed to standard laparoscopic ("keyhole" or "mini") surgery. Since I am an internist and neither article will affect my practice or income, I feel  can comment on them without bias (outside my usual inquisitorial examination of the evidence presented in research papers, a habit than has only been intensified by my over 20 years of reviewing articles). This blog will discuss the possible aspirin-colon cancer reduction link, and the next will discuss robotic surgery.

Let us look at the aspirin-colon cancer article first. As some background, let me inform my non-medical readers that it appears that it takes 5 years from the time a polyp first develops in the colon until it becomes cancerous (and I am here excluding any familial cases). Since as the polyps enlarge they tend to put drops of blood into the stool, the first screening for colon cancer that was shown to reduce the death rate from colon cancer was the annual test for blood in the stool. When I started practice in the early 1980"s, it was known that  five year examinations of the distal 25 centimeters of the colon by a rigid proctoscope detected enough cancers to reduce the death rate from colon cancer, and this became a standard practice for me. One curious fact that was noted and unexplained was that even though only a minute part of the distal colon was examined, fatal cancers originating in the proximal colon were also reduced (although not by as much). The proctoscope, or rigid signoidoscopy was soon replaced by the flexible sigmoidoscope, which reached further into the distal colon. This examination, if given every 5 to 10 years, also reduced colon cancer deaths in the proximal as well as the distal colon, but, again the incidence of cancers in the distal colon were much more strongly affected, than that  of cancers in the proximal colon .

A few years ago, a 5 year retrospective study of 5,000 female American nurses was published. The study showed that the frequent use of NSAID's (usually Advil or Alleve) reduced the incidence of and death from colon cancer. (I might here mention that a parallel 5 year study of females placed on a low fat diet showed no reduction in the incidence of either colon or breast cancer, but people still seem to think, without any hard evidence, that animal fat is carcinogenic for humans.)  This study led to the Vioxx study, where Merck hoped that they could show that Vioxx, another NSAID, also reduced the incidence of colon cancer, so they could get FDA approval to market it as such. Unfortunately, the initial data showed an increase in cardiovascular events, so the study  was terminated, as was Vioxx. I leave it to the audience to search the published reports to see which NSAID is the safest and which is the most apt to produce cardiac events. The last time I reviewed the subject (and this may not be true now) prescription Celebrex was the safest anti-inflammatory , and OTC Alleve/Naprosyn had the highest incidence of cardiac events.

So now we come to the latest study, published in Lancet (Vol. 376, Nov. 20, 2010, pp1741-1750). The study found that a dose of 75 mg. of daily aspirin (a baby aspirin has 81 mg) reduced the incidence and mortality of colon cancer, and the benefit was highest for proximal cancers. A few caveats. This article was the result of pooling 5 different studies, and in none of the studies was colon cancer the endpoint. Furthermore, the pooling showed a much greater effect in men than in women.We also think we know that aspirin reduces the incidence of colon polyps by suppressing COX-2, and tumors in the distal colon seem to have greater interaction with COX-2 receptors than do proximal tumors. It also did not compare the use of daily aspirin with q. 5 year colonoscopes with regard to reduction in the incidence of colon cancer.

Now when my patients ask me about  how to apply the results of this study to their own medical lives, I will reply as follows: There is now some evidence that taking a daily 81 mg. (children's) aspirin will reduce your chance of getting colon cancer, but no one has compared the % reduction achieved with aspirin with that achieved by either an annual stool-for-blood test or q. 5-10 years colonoscopy, and daily aspirin use increases your risk of GI bleeding. We also have absolutely no idea if adding daily ASA to the suggested routine of colonoscopy plus stool-for-blood  will have a positive synergistic effect. On the other hand, it is evident that if aspirin does have a preventive effect, it is greater for proximal colon tumors than distal tumors, and proximal tumors are the ones least likely to be detected by either colonoscopy or stool-for-blood. I would also suggest that if they absolutely refuse to ever have a colonoscopy then a daily children's aspirin is probably a good idea.


  1. Thanks Dr. Thomas for the elucidation. Would enteric coated aspirin be a better option than regular aspirin if we consider the GI bleeding risk?
    Also, is it possible that GI bleeding due to aspirin might interfere with the interpretation of fecal occult blood test?

  2. There have been two studies, neither of which was able to show that enteric coated aspirin caused less bleeding than regular aspirin. This was further validated by the observation that NSAID's such as Advil can cause bleeding in the small and large bowel as well as in the stomach.
    There is one study that showed that if you take 20 mg. Pepcid twice a day when you are taking any aspirin, you decrease the risk of GI bleeding.

  3. And patients are instructed to avoid ASA for one week before the fecal occult blood test, and any other NSAID for 72 hours.