Featured Research

from universities, journals, and other organizations

Aspirin Decreases Genetic Mutations Associated With Inherited Colon Cancer

Date:
September 15, 1998
Source:
Jefferson Medical College
Summary:
Aspirin may prevent the development of a particular type of common hereditary colorectal cancer in those at high risk for the disease. Scientists at Jefferson Medical College believe they’ve uncovered a molecular mechanism by which aspirin interferes with colorectal cancer development in those individuals who carry particular gene mutations that makes them very likely to get the disease.

A new study suggests that aspirin will be a useful chemopreventative for Hereditary Colon Cancer patients

Aspirin may prevent the development of a particular type of common hereditary colorectal cancer in those at high risk for the disease.

Scientists at Jefferson Medical College believe they’ve uncovered a molecular mechanism by which aspirin interferes with colorectal cancer development in those individuals who carry particular gene mutations that makes them very likely to get the disease.

"Aspirin is a well known prophylaxis for cancer," says molecular geneticist Richard Fishel, Ph.D., professor of microbiology and immunology at the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, who with Josef RŸschoff, M.D., of the University of Regensburg, Germany, led the research. "The new twist is that aspirin suppresses the accumulation of mutations that are the cause of a common inherited cancer." Similar mutations are found in 5-10% of sporadic colorectal, endometrial and ovarian cancers.

Their work appears September 15 in the Proceedings of the National Academy of Sciences.

Drs. Fishel, RŸschoff and their colleagues examined human colon cancer cell lines with defective mismatch repair genes, which are necessary to fix normal cell damage that occurs when cells divide and multiply. These mismatch repair genes were discovered by Dr. Fishel and Dr. Richard Kolodner (now at the Ludwig Institute for Cancer Research in San Diego) in 1993 to be the cause of the most common form of hereditary cancer known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

The scientists then treated the colon tumor cells with two drugs: aspirin and sulindac, which are both nonsteroidal anti-inflammatory drugs and known cancer preventatives. They found that the drugs largely suppressed the genetic instability that underlies the development of cancer in HNPCC.

"Our results appear to suggest a very simple treatment for a common hereditary cancer predisposition syndrome," Dr. Fishel says.

For a normal cell to become a tumor cell, many mutations must occur. The accumulation of multiple mutations implies genetic instability. Aspirin suppresses that accumulation of these mutations. "Even sporadic [non-hereditary] cancer may be considered to be a genetic disease because a large number of mutations must accumulate in the tumor cells," says Dr. Fishel "Aspirin screens for cells that are genetically stable, providing a true genetic selection against such forms of cancer.

"The important point here is that this [Aspirin] is an inexpensive over-the-counter drug that anyone can take. When we first discovered the connection of mismatch repair genes to hereditary cancer there was really nothing we could recommend to families besides increased [and sometimes painful] surveillance. Now we may actually be able to prevent the disease in these individuals and allow them to lead a normal life."

According to Dr. Fishel, other researchers have shown that taking aspirin reduces the incidence of sporadic colorectal cancer in the population. "That tells you that in some fraction of the population, aspirin has some efficacy. Our results would suggest that the tumors which are most affected by aspirin may arise from having damaged mismatch repair genes. In other words, you are really only suppressing the class of tumors that are caused by having these altered genes."

Non-Steroid anti-inflammatory drugs such as aspirin and sulindac are generally thought to work through the prostaglandin pathway via cyclooxygenase (COX). The study by Drs. RŸschoff and Fishel suggests that COX is not involved.

Scientists would like to find substances that reduce the effects of environmental toxicities. Aspirin looks like it will be one of them. At least for the mutations that occur as a result of specific genetic defects associated with hereditary and some sporadic tumor cells.

When mismatch repair genes go awry, the result is commonly colon cancer. Such genes are part of the intricate molecular machinery that fixes the cellular DNA when for some reason, cell replication doesn’t work correctly. According to Dr. Fishel, MSH2 and MLH1 are the most frequently altered genes in HNPCC, which accounts for some 10 to 15 percent of all colorectal cancers. A mismatch of the DNA nucleotides, or building blocks, may occur during cell replication. In replication, precise nucleotide pairing is essential. In human cells, it is a protein complex containing hMSH2 that attaches to mismatched nucleotides. The cellular repair machinery, with hMLH1, then orchestrates the correction of these errors. "Without hMSH2 or hMLH1 the cellular DNA becomes unstable, errors accumulate and the result is cancer," Dr. Fishel explains.

"Now the question is, will it work in humans?" says Dr. Fishel. "We already know there is some efficacy in humans. We didn’t know why--this work at least partially answers that question."

"This is an important step for cancer prevention in HNPCC", says Dr. Henry Lynch of Creighton University and one of the founders of HNPCC (also called Lynch's Syndrome). "Drs. Fishel and RŸschoff's work provides a basic research foundation to helping individuals with this devastating disease."

One next step already underway is a clinical trial in Europe to study the effectiveness of higher doses of aspirin in preventing hereditary colorectal cancer. Dr. Lynch, Dr. Fishel, and Dr. John Burn (University of Newcastle, England and leader of the European Study) are currently organizing the international hereditary colorectal cancer prevention trial using aspirin.

There is a downside to aspirin and sulindac: they have already been shown to harbor some gastrointestinal toxicity and liver toxicity, respectively. "In the future, we would like to understand the specific mechanism and the exact target for the genetic suppression as well as minimize the toxicity," Dr. Fishel says. "Not everyone can take aspirin. This has to be done the right way and in consultation with a physician."

According to the American Cancer Society, colon and rectal cancer is the third most common cancer in the nation, with some 200,000 new cases diagnosed annually. Approximately 30,000 people die each year from colon and rectal cancer. Between 15-30% of colorectal cancers appear to have a hereditary origin and approximately 50% of those involve germline mutation of the human mismatch repair genes.


Story Source:

The above story is based on materials provided by Jefferson Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Jefferson Medical College. "Aspirin Decreases Genetic Mutations Associated With Inherited Colon Cancer." ScienceDaily. ScienceDaily, 15 September 1998. <www.sciencedaily.com/releases/1998/09/980915075805.htm>.
Jefferson Medical College. (1998, September 15). Aspirin Decreases Genetic Mutations Associated With Inherited Colon Cancer. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/1998/09/980915075805.htm
Jefferson Medical College. "Aspirin Decreases Genetic Mutations Associated With Inherited Colon Cancer." ScienceDaily. www.sciencedaily.com/releases/1998/09/980915075805.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins