Overexpression of epidermal growth factor in the liver induces transformation to hepatocellular carcinoma in animal models.
Polymorphisms in the epidermal growth factor gene modulate epidermal growth factor levels.
Dr Kenneth Tanabe and colleagues from France assessed the relationship among human epidermal growth factor gene single-nucleotide polymorphism, epidermal growth factor expression, and risk of hepatocellular carcinoma.
|There was a 4-fold odds of hepatocellular carcinoma in G/G patients |
|Journal of the American Medical Association|
The team examined molecular mechanisms linking the 61*G allele polymorphism to epidermal growth factor expression in human hepatocellular carcinoma cell lines and human liver tissue.
The research team undertook a case-control study involving 207 patients with cirrhosis at the Massachusetts General Hospital between 1999 and 2006.
The researchers also conducted a validation case-control study involving 121 patients with cirrhosis at Hôpital Paul Brousse between 1993 and 2006.
The team used restriction fragment-length polymorphism to determine the epidermal growth factor gene polymorphism genotype.
Logistic regression analysis was used to assess the association between the epidermal growth factor polymorphism and hepatocellular carcinoma risk.
The researchers found mechanisms by which the epidermal growth factor gene polymorphism modulates epidermal growth factor levels.
The team also identified associations among epidermal growth factor gene polymorphism, epidermal growth factor levels, and hepatocellular carcinoma.
The researchers found that transcripts from the epidermal growth factor 61*G allele exhibited more than a 2-fold longer half-life than those from the 61*A allele.
The epidermal growth factor secretion was 2.3-fold higher in G/G hepatocellular carcinoma cell lines than A/A cell lines.
Serum epidermal growth factor levels were 1.8-fold higher in G/G patients than A/A patients, and liver epidermal growth factor levels were 2.4-fold higher in G/G patients than A/A patients.
The researchers noted that among the 207 patients with cirrhosis in the Massachusetts study population, 59 also had hepatocellular carcinoma.
Analysis of the distribution of allelic frequencies revealed that there was a 4-fold odds of hepatocellular carcinoma in G/G patients compared with A/A patients in the Massachusetts study population.
The team used logistic regression analysis to demonstrate that the number of copies of G was significantly associated with hepatocellular carcinoma.
This association remained significant after adjusting for age, sex, race, etiology, and severity of cirrhosis.
The significant association was validated in the French patients with alcoholic cirrhosis and hepatocellular carcinoma.
Dr Tanabe's team concluded, "The epidermal growth factor gene polymorphism genotype is associated with risk for development of hepatocellular carcinoma in liver cirrhosis through modulation of epidermal growth factor levels."