Gene variation may increase risk of liver tumor in cirrhosis patients

January 2nd, 2008 - 5:21 pm ICT by admin  


Washington, Jan 2 (ANI): Scientists have found that a single alteration in the epidermal growth factor (EFG) gene may make patients with cirrhosis susceptible to hepatocellular carcinoma (HCC), a liver tumour that is the third leading cause of cancer death.

If these results are confirmed, this EGF variation could be used to determine which cirrhotic patients should be screened more intensively for tumor development, said lead researcher Dr. Kenneth Tanabe, chief of Surgical Oncology at the Massachusetts General Hospital (MGH) Cancer Center.

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, he added.

HCC is usually caused by the infection with the hepatitis B or C viruses, and currently there is no effective treatment for HCC patients.

Several previous animal studies had revealed that elevated levels of the EGF gene in the liver might lead to tumour development, and that blocking the proteins receptor might prevent development of liver cancer.

The current studys objective was to find out whether cirrhotic patients having higher EGF levels are more prone to liver cancer, and to determine the effect of a particular inherited gene on EGF levels in such patients.

The researchers focussed on a known variation in the EGF gene, which increases EGF secretion in blood cells and increases the risk for malignant melanoma. This variation is characterised by the presence of the nucleotide guanine (G), instead of the more common adenine (A), in a particular location.

A single copy of the gene is inherited by an individual from each parent, and therefore has this gene with either two copies of A (A/A), two copies of G (G/G), or one copy of each (A/G).

According to the genetic analysis of liver tumour cell lines, messenger RNA transcribed from DNA strands with the G allele was more stable than that transcribed from the A version. This explained the reason behind higher secretion levels of EGF in gene with two G copies.

The researchers then studied tissue samples from all patients in the MGH Cancer Center Tumor Bank who had cirrhosis.

They found that out of 207 patients with cirrhosis, with a majority infected with the hepatitis C virus, 59 had HCC.

Patients having at least one copy of the G nucleotide were at a higher risk of developing HCC as compared with A/A patients. The risk was double for patients with one G, and around four times for those with two G alleles.

Tissue analysis showed that, in all three genotypes, EGF levels were highest in the G/G patients, as was the activation of the EGFR receptor. Also, blood levels of EGF were highest in those having two copies of the G allele.

In order to confirm their findings in a different patient population, the MGH team worked with colleagues from the Paul Brousse Hospital in Paris. They took samples from this group, all of whom had alcoholic cirrhosis.

The researchers found that the risk of developing liver tumour was thrice in patients with the G/G version of the EGF gene as compared to A/A patients.

They also observed that the G allele was more common among Asian patients, supporting the fact that more than half the cases of HCC worldwide occur in China.

The study is published in the recent issue of the Journal of the American Medical Association. (ANI)

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