Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene variation may elevate risk of liver tumor in patients with cirrhosis

03.01.2008
Growth factor pathway may be target for preventive treatment

A particular gene variation appears to significantly increase the risk that individuals with cirrhosis of the liver will go on to develop hepatocellular carcinoma (HCC), a liver tumor that is the third leading cause of cancer death. In the January 2 Journal of the American Medical Association, researchers from Massachusetts General Hospital (MGH) Cancer Center and colleagues in France describe finding that a single alteration in the epidermal growth factor (EFG) gene may greatly increase the risk of developing HCC.

“If these results are confirmed, this EGF variation could be used to determine which cirrhotic patients should be screened more intensively for tumor development,” says Kenneth Tanabe, MD, chief of Surgical Oncology at the MGH Cancer Center, the study’s lead author. “In addition, the molecular pathway controlled by EGF and its receptor EGFR – which is known to be important in several types of cancer – appears to be an excellent target for chemoprevention studies. This is a deadly cancer and so progress in prevention and early detection is critically important.”

HCC is the sixth most common solid tumor worldwide and most commonly develops in individuals with cirrhosis, which may be caused by infection with the hepatitis B or C viruses. There are currently no effective treatments for most HCC patients, so there is considerable interest in strategies that may prevent development of the tumor.

EGF’s normal function is to stimulate tissue growth. Animal studies have shown that elevated levels of this protein in the liver lead to tumor development and that blocking the protein’s receptor can prevent development of liver cancer. The current study was designed to determine whether cirrhotic patients with higher EGF levels are at greater risk for liver cancer and to determine the influence of a particular inherited gene on EGF levels in cirrhotic patients.

The researchers focused on a known variation in the EGF gene – the presence of the nucleotide guanine (G) instead of the more common adenine (A) in a particular location – which has been shown to increase EGF secretion in blood cells and raise the risk for malignant melanoma. Individuals inherit one copy of the gene from each parent and therefore have this gene with either two copies of A (A/A), two copies of G (G/G), or one copy of each (A/G). Genetic analysis of liver tumor cell lines showed that messenger RNA transcribed from DNA strands with the G allele was more stable that that transcribed from the A version, which could explain why cells with two G copies tend to secrete higher levels of EGF.

The researchers then studied tissue samples from all patients in the MGH Cancer Center Tumor Bank who had cirrhosis. Among the 207 patients with cirrhosis, most of whom were infected with the hepatitis C virus, 59 also had HCC. Patients with at least one copy of the G nucleotide had a significantly higher risk of developing HCC than did A/A patients – ranging from a more than twofold increase for those with one G to an over fourfold increase for those with two G alleles. In all three genotypes, tissue analysis showed that EGF levels were highest in the G/G patients, as was activation of the EGFR receptor. In addition, blood levels of EGF were highest in those with two copies of the G allele.

To confirm these finding in a different patient population, the MGH team worked with colleagues from the Paul Brousse Hospital in Paris. Samples from this group, all of whom had alcoholic cirrhosis, also showed that patients with the G/G version of the EGF gene had a significantly greater risk of developing the liver tumor than did the A/A patients, in this instance an almost threefold risk increase.

In both the MGH and French study groups, controlling for factors such as age and gender did not change the increased risk associated with the G allele. While both groups primarily consisted of Caucasian patients, in the MGH group, it was noted that the G allele was more common among Asian patients; and it is well known that more than half the cases of HCC worldwide occur in China.

“We now need to prospectively study EGF levels in cirrhotic patients, to see if elevated levels will correlate with a greater risk of developing HCC, and look at factors such as diet, drugs or ethnicity that may modulate EGF levels,” Tanabe says. “I think this is a terrific opportunity to see if targeting a specific pathway will prevent HCC in this group of patients, who are at risk for liver cancer because of their cirrhosis.” Tanabe is an associate professor of Surgery at Harvard Medical School.

Stacy Neale | EurekAlert!
Further information:
http://www.mgh.harvard.edu/

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Early organic carbon got deep burial in mantle

25.04.2017 | Earth Sciences

A room with a view - or how cultural differences matter in room size perception

25.04.2017 | Life Sciences

Warm winds: New insight into what weakens Antarctic ice shelves

25.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>