An Ounce of Prevention

Colorectal cancer is among the leading causes of cancer death in the United States. While most patients develop this disease over a period of decades, associated with an accumulation of genetic mutations (elegantly described by Burt Vogelstein, PhD at Johns Hopkins), a small percentage of patients have a genetic predisposition for this cancer. Among these are those people that carry the familial adenomatous polyp syndrome (FAPS) and those who carry mismatch repair mutations know as Lynch syndrome.

It is the latter group who are the subject of a report in the October issue of the English journal Lancet. In this study, known as the CAPP2 trial, patients with Lynch syndrome received either placebo or 600mg of aspirin per day (the equivalent of two tablets). The results reveal a statistically significant reduction of colon cancer that clearly favored the aspirin group.

To put this in perspective, this dramatic improvement in the highest risk population didn’t come about as the result of a new signal transduction inhibitor or a monoclonal antibody. Instead, it came from the simple administration of one of mankind’s earliest medicinal substances. I applaud these English investigators in conducting this study of 861 patients.

What is most laudatory is that the intervention, while highly effective, is so inexpensive. In an era of proprietary medications and the promotion of expensive new interventions, it is indeed refreshing to read the results of a well-conducted study using an intervention available to all.

Data generated more than two decades ago established the benefit of non-steroidal anti-inflammatory drugs like aspirin for the prevention of colorectal cancer. It is gratifying that this simple intervention has additional scientific support both for those with high-risk predisposition, as well as other patients at risk for this relatively common, yet potentially lethal, malignancy.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

4 Responses to An Ounce of Prevention

  1. linda says:

    Dr. N —
    I read a similar study on ovarian cancer several years ago and started taking daily aspirin because I had had ovarian cysts.
    But when I mentioned it to my PCP she laughed at me and said my research was “so interesting.”
    I wish I had continued taking it as last year I was diagnosed with late stage OVCA.
    Is there any indication aspirin is at all effective in preventing recurrence?
    thank you
    Linda

  2. Dr. Nagourney

    Speaking of genetic mutations and a small percentage of patients having a genetic predisposition for this cancer, the Huntsman Cancer Institute in Utah reported that thousands of people across the country may have a mutation that spread widely from a couple’s descendants branched apart over many generations.

    I have an indirect interest in this because my wife’s ancestors on her mother’s side came from London, England to Onancock, VA as passengers on the ship Deliverance around 1608.

    The Huntsman researchers said a married couple who sailed to America from England around 1630 are the reason why thousands of people in the United States are at higher risk of a hereditary form of colon cancer.

    Using a genetic fingerprint, a U.S. team traced back a so-called founder genetic mutation to the couple found among two large families currently living in Utah and New York. The fact that this mutation can be traced so far back in time suggests it could be carried by many more families in the United States than is currently known.

    They identified the mutation as attenuated familial adenomatous polyposis (AFAP), which makes people more prone to developing polyps that can cause colon cancer. The study highlights the need to pay attention to family history, which my wife’s family has.

    Your thoughts.

  3. Elaine L. says:

    I find your question fascinating, Greg.

    Dr. N, it is indeed wonderful, that the aspirin study was done, since I have heard much in the media regarding aspirin and the reduction of colon cancer.

  4. Paul B says:

    It would be good for the US oncology experts to do a similar study on Vitamin D. Dr. Garland at UCSD epidemiological research shows we could reduce colon and many cancer incidence by 50% with good levels of Vitamin D. The research at Creighton University already showed a wide range of cancer incidence of cancer reduced 70% if you did not include the first year cancers and 50% if you did. It is related to about 15 different cancers.
    The aspirin works because the Cox 2 enzymes are involved in promoting tumor growth. Since aspirin blocks cox 1 and cox 2 it should help. Same reason Celebrex works for familial polyposis Vitamin D inhibits polyp and tumor growth. If oncology was not such a big profitable business, we would see more readily available inexpensive preventive treatments promoted here. If oncologists would use labs like Rational Therapeuics maybe we would be more effective with cancer therapy. If we also would start looking at the host response to cancer development instead of just killing the cancer, we might have better survival rates someday.

    Just think what would happen to the cancer rate if we had a national program to prevent cancer with everyone on some aspirin, and Vitamin D. Vitamin D controls 2000 cell regulatory genes. It is possible it could attenuate the genetic expression of the familial polyposis.

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