Aspirin Chemoprevention Now Recommended in Lynch Syndrome

Individuals with Lynch syndrome have an above average lifetime risk of a host of cancers- cancer risk that can be dramatically reduced with an inexpensive form of complementary therapy.  Please consider asprin therapy as chemoprevention and read the article linked below.

1) "Lynch syndrome, a hereditary disorder that affects genes involved in DNA repair, predisposes affected individuals to developing cancer at a young age. It affects about 1 person in every 1000, and about half of those affected develop cancer, most commonly colorectal and uterine."

2) "About 15% of the group taking aspirin developed cancer, compared with 30% of those not taking aspirin, he noted.

The reduction in incidence for colorectal cancer — the primary end point — was significant. There was also "substantial protection" against other Lynch-syndrome-associated cancers, (e.g., small intestinal, endometrial, ovarian, kidney), although this did not reach statistical significance.

http://www.medscape.com/viewarticle/752436?src=mpnews&spon=7

"Lynch syndrome (HNPCC or Hereditary nonpolyposis colorectal cancer ) is an autosomal dominant genetic condition which has a high risk of colon cancer^[1] as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair."

"Individuals with HNPCC have about an 80% lifetime risk for colon cancer. Two-thirds of these cancers occur in the proximal colon. The mean age of colorectal cancer diagnosis is 44 for members of families that meet the Amsterdam criteria. Also, women with HNPCC have a 80% lifetime risk of endometrial cancer. The average age of diagnosis of endometrial cancer is about 46 years. Among women with HNPCC who have both colon and endometrial cancer, about half present first with endometrial cancer. In HNPCC, the mean age of diagnosis of gastric cancer is 56 years of age with intestinal-type adenocarcinoma being the most commonly reported pathology. HNPCC-associated ovarian cancers have an average age of diagnosis of 42.5 years-old; approximately 30% are diagnosed before age 40 years. Other HNPCC-related cancers have been reported with specific features: the urinary tract cancers are transitional carcinoma of the ureter and renal pelvis; small bowel cancers occur most commonly in the duodenum and jejunum; the central nervous system tumor most often seen is glioblastoma."

http://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer

Aspirin Chemoprevention Now Recommended in Lynch Syndrome

"This is a huge breakthrough in terms of cancer prevention," Dr. Morrison said in a statement. "Not only does it show we can reduce cancer rates and ultimately deaths, it opens up other avenues for further cancer prevention research."

In the future, the team intends to "look at the use of aspirin in the general population as a way of reducing the risk of bowel cancer," he added. This is not currently recommended, mainly because of concerns about toxic effects, according to an accompanying editorial. The editorialists add that this trial, in isolation, does not move that indication any further along.

However, for the specific population of individuals with Lynch syndrome, the results are "compelling," write editorialists Andrew Chan, MD, from Massachusetts General Hospital in Boston, and Scott Lippman, MD, from the University of Texas M.D. Anderson Cancer Center in Houston. They agree with the study authors on the implications of this research.

"The results provide a strong rationale for routine use in individuals with Lynch syndrome," the editorialists note.

First Randomized Trial

The Colorectal Adenoma/Carcinoma Prevention Programme 2 (CAPP2) is the first double-blind randomized trial to study aspirin chemoprevention that has colorectal cancer as the primary end point. It was conducted from 1999 to 2005, and assigned 861 participants in 16 countries to take either aspirin (600 mg daily) or placebo for up to 4 years.

The first analysis of the trial data, in 2007, showed no difference in the incidence of colorectal cancer between the 2 treatment groups.

However, by the time another analysis was conducted, in 2010, there had been several more cases of cancer, and a significant difference was seen between the aspirin and placebo groups, with an overall 44% reduced incidence of colorectal cancer.

When the researchers focused specifically on individuals who had taken aspirin for at least 2 years (about 60% of the group), the difference was even more pronounced, showing a 63% reduction in the incidence of colorectal cancer (10 cases in the aspirin group vs 23 in the placebo group).

A surprising finding from this study is that although there was a reduction in the incidence of colorectal cancer, there was no difference between the 2 groups in the incidence of polyps, which are precursors to cancer. It appears that the individuals who were taking aspirin still developed polyps, but the polyps did not become cancerous, presumably because of the effects of aspirin.

Consistent With Previous Data

"The outcome is consistent with more than 2 decades of observational data showing that the risk of colorectal cancer is halved in regular aspirin consumers," note the authors.

"Our results, taken in conjunction with recent research, provide a basis for the recommendation of aspirin chemoprevention in Lynch syndrome as a standard of care," said lead author Sir John Burn, MD, FRCOP FRCPCH, FRCOG, FMedSci, professor of clinical genetics at Newcastle University, United Kingdom.

"We have succeeded in showing the benefits of aspirin because we had a lot of long-term data and because Lynch syndrome is associated with the rapid development of cancer," he said in a statement.

There might be implications here for the general population, he explained, but "before anyone begins to take aspirin on a regular basis, they should consult their doctor, as aspirin is known to bring with it a risk of stomach complaints, including ulcers." However, "if there is a strong family history of cancer, then people may want to weigh the cost/benefits, particularly because these days drugs that block acid production in the stomach are available over the counter," he added.

The case for the prescription of aspirin to this high-risk group is clear.

A summary published in the Lancet asserts that "in the context of the published literature, the trial provides clear evidence that aspirin is an effective chemopreventive agent in hereditary cancer, with an effect equivalent to that achieved with surveillance colonoscopy. The case for the prescription of aspirin to this high-risk group is clear."

Questions remain about the mechanism of action of the delayed effect that is seen, and therefore about the dose and duration of aspirin to be used, according to the summary. Indirect evidence suggests that a lower dose of aspirin has a similarly protective effect. Another trial (CAPP3, currently recruiting) will compare different doses of aspirin in patients with Lynch syndrome.

"In the meantime, clinicians should consider the prescription of aspirin for all individuals judged to be at high risk of colorectal cancer, but taking appropriate measures to minimize adverse effects," the summary concludes.

To read the entire article-

http://www.medscape.com/viewarticle/752436?src=mpnews&spon=7

Do you have Lynch Syndrome?  Do you take asprin for cancer prevention?

Thank you

David Emerson