Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Beyond associations: Colorectal cancer culprit found

24.04.2009
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.

Media contacts:

Richard S. Houlston, Ph.D. is available for more information by contacting Jane Bunce, Science Press Officer at The Institute of Cancer Research, (jane.bunce@icr.ac.uk; +44 207 153 5106).

Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (calicchi@cshl.edu; +1-516-422-4012).

About the article:

The manuscript will be published online ahead of print on April 24, 2009. Its full citation is as follows: 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 Res doi:10.1101/gr.092668.109.

About Genome Research:

Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.

Genome Research issues press releases to highlight significant research studies that are published in the journal.

Peggy Calicchia | EurekAlert!
Further information:
http://www.cshl.edu
http://www.genome.org

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>