Featured Research

from universities, journals, and other organizations

Beyond Associations: Colorectal Cancer Culprit Found

Date:
May 1, 2009
Source:
Cold Spring Harbor Laboratory
Summary:
Genetics plays a key role in risk for colorectal cancer, the second leading cause of cancer-related deaths in the United States. Several genetic markers are associated with the disease, but finding the biological events that lead to cancer is much more difficult. In a new study, scientists identified a common genetic variation associated with CRC risk and its functional implications, shedding new light on the basis of this disease.

Genetics plays a key role in determining risk for colorectal cancer, the second leading cause of cancer-related deaths in the United States. Several common genetic markers have been found to be associated with the disease, but finding the biological events that lead to cancer can be much more difficult.

In a study published online in Genome Research, scientists have identified a common genetic variation associated with the risk of colorectal cancer and its functional implications, shedding new light on the basis of this deadly disease.

Hunting down the genes that underlie diseases such as colorectal cancer is extremely difficult, owing to the genetic heterogeneity of cancer cells. Numerous mutations can be found in a cancer cell, but the key to developing new treatments and therapies is to identify the variants that cause the disease hidden amongst many mutations that are simply bystanders. Recently, researchers have been aided in this search by the genome-wide association study (GWAS), a technique that scans the genome for known common genetic variants, also known as single nucleotide polymorphisms, or "SNPs," that are more prevalent in patients with a specific disease. However, a SNP associated with a disease is not necessarily the culprit – but it raises a red flag that something important is nearby.

In this study, an international team of researchers led by Dr. Richard Houlston of The Institute of Cancer Research in the United Kingdom have delved into the biology underlying common variants on chromosome 18 that his group recently found to be associated with colorectal cancer in a GWAS. They sequenced the region of DNA surrounding these markers in a large group of colorectal cancer cases and controls, identifying all variants residing in this chromosomal region common to colorectal cancer patients.

Houlston and colleagues then focused on the novel variant most strongly associated with colorectal cancer, and found that it resides in a DNA sequence that is conserved in many other species – so well conserved that they were able to use xenopus frogs as a model organism to test the biological consequences of this SNP. The group found that the SNP causes the expression of a nearby gene, called SMAD7, to decrease. SMAD7 is an inhibitory regulator of TGF-beta signaling. If cellular levels of SMAD7 are down, critical signaling events could be set into motion, leading the cell on the path to cancer. This result is particularly important because disruption of SMAD7 expression has been previously implicated in progression of colorectal cancer. Taken together with this knowledge, their observation supports a direct role for SMAD7 in cancer progression, and very likely the causal basis for colorectal cancer risk associated with this chromosomal region.

Houlston explained, "Our efforts show that many different methodologies are required to close in and identify disease-causing variants identified through genome-wide association studies." Their work specifically exemplifies the combination of genetic and functional analyses, including regenotyping, resequencing, and use of model organisms, needed to approach the biological mechanism of cancer. By identifying the true causal variants and understanding the biological basis for cancer risk associated with those variants, researchers will be able to design better screening strategies and more effective therapies for patients.

Scientists from the Institute of Cancer Research (Sutton, UK), Centro Andaluz del Biologia del Desarollo (Seville, Spain), and Leiden University (Leiden, The Netherlands) contributed to this study.

This work was supported by Cancer Research UK and the European Union.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Pittman AM, Naranjo S, Webb E, Broderick P, Lips EH, van Wezel T, Morreau H, Sullivan K, Fielding S, Twiss P, Vijayakrishnan J, Caseres F, Qureshi M, Gomez-Skarmeta JL, Houlston RS. The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression. Genome Research, 2009; DOI: 10.1101/gr.092668.109

Cite This Page:

Cold Spring Harbor Laboratory. "Beyond Associations: Colorectal Cancer Culprit Found." ScienceDaily. ScienceDaily, 1 May 2009. <www.sciencedaily.com/releases/2009/04/090423180227.htm>.
Cold Spring Harbor Laboratory. (2009, May 1). Beyond Associations: Colorectal Cancer Culprit Found. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2009/04/090423180227.htm
Cold Spring Harbor Laboratory. "Beyond Associations: Colorectal Cancer Culprit Found." ScienceDaily. www.sciencedaily.com/releases/2009/04/090423180227.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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