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 Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth
01.03.2017 | Hochschule für Angewandte Wissenschaften Hamburg

nachricht Researchers Imitate Molecular Crowding in Cells
01.03.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

A better way to measure the stiffness of cancer cells

01.03.2017 | Health and Medicine

Exploring the mysteries of supercooled water

01.03.2017 | Physics and Astronomy

Research team of the HAW Hamburg reanimated ancestral microbe from the depth of the earth

01.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>