G/G allele raises probability of cirrhosis patients developing HCC by fourfold, according to JAMA paper.

An SNP in the epidermal growth factor (EGF) gene appears to significantly increase the risk that individuals with cirrhosis of the liver will go on to develop hepatocellular carcinoma (HCC), according to investigators at Massachusetts General Hospital (MGH) Cancer Center.

The researchers focused on a known variation in the EGF gene, the presence of the nucleotide guanine instead of the more common adenine in a particular location. This mutation has been shown to increase EGF secretion in blood cells and raise the risk for malignant melanoma.

Genetic analysis of liver tumor cell lines showed that mRNA transcribed from DNA strands with the G allele were more stable than those transcribed from the A version. This could explain why cells with two G copies tend to secrete higher levels of EGF, the research team reports.

The scientists then studied tissue samples from all patients in the MGH Cancer Center Tumor Bank who had cirrhosis. Among the 207 patients with cirrhosis, 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, according to the investigators. The risk reportedly ranged 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.

To confirm these findings in a different patient population, the MGH team worked with colleagues from the Paul Brousse Hospital. 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 occurred.

The research is published in the January 2 issue of the Journal of the American Medical Association.

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