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Gene variation may elevate risk of liver tumor in patients with cirrhosis
Date:1/1/2008

e 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,
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Contact: Stacy Neale
sneale@partners.org
617-643-3907
Massachusetts General Hospital
Source:Eurekalert

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