Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Gene Variation may Elevate Risk of Liver Tumor in Patients with Cirrhosis

Published: Tuesday, January 08, 2008
Last Updated: Tuesday, January 08, 2008
Bookmark and Share
A single alteration in the epidermal growth factor (EFG) gene may greatly increase the risk of developing hepatocellular carcinoma, researchers say.

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.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,700+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

First Gene that Causes Mitral Valve Prolapse Identified
An international research collaboration led by MGH investigators has identified the first gene in which mutations cause the common form of mitral valve prolapse, a heart valve disorder that affects almost 2.5 percent of the population.
Tuesday, August 11, 2015
Evo-Engineered CRISPR-Cas9s Hit More Gene-Editing Targets
Scientists have engineered a more effective CRISPR- Cas9 system paving the way for more advanced applications.
Wednesday, June 24, 2015
Genetic Signals Reflect the Evolutionary Impact of Cholera
Study identifies regions of genome associated with cholera susceptibility in Bangladesh.
Monday, July 08, 2013
Powerful Gene-Editing Tool Appears to Cause Off-Target Mutations in Human Cells
Results indicate need to improve precision of CRISPR-Cas RNA-guided nucleases.
Wednesday, June 26, 2013
Mass. General, Duke Study Identifies Two Genes that Combine to Cause Rare Syndrome
Mutations in genes that regulate cellular metabolism found in families with ataxia, dementia and reproductive failure.
Monday, May 13, 2013
Circulating Tumor Cells can Reveal Genetic Signature of Dangerous Lung Cancers
MGH-developed device promises improvements in targeted therapy, treatment monitoring.
Friday, July 04, 2008
Scientific News
Removing 62 Barriers to Pig–to–Human Organ Transplant in One Fell Swoop
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Gene Editing Could Enable Pig-To-Human Organ Transplant
The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them.
Antioxidants Cause Malignant Melanoma to Metastasize Faster
Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice.
UC San Diego Team Up with Illumina to Speed-Read Your Microbiome
Data analysis app accelerates studies aimed at using microbes to predict, diagnose and treat human diseases.
Paving the Way for Diamonds to Trace Early Cancers
Researchers from the University of Sydney reveal how nanoscale 'diamonds' can light up early-stage cancers in MRI scans.
Researchers Develop Classification Model for Cancers Caused by KRAS
Most frequently mutated cancer gene help oncologists choose more effective cancer therapies.
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Shaking Up the Foundations of Epigenetics
Researchers at the Centre for Genomic Regulation (CRG) and the University of Barcelona (UB) published a study that challenges some of the current beliefs about epigenetics.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos