A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

Abstract

BackgroundA single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been associated with increased risk of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the relationship between the EGF SNP genotype and the development and prognosis of HCC, in a Japanese population.MethodsRestriction fragment-length polymorphism was used to determine the presence of the EGF SNP genotype in 498 patients, including 208 patients with HCC. The level of EGF messenger ribonucleic acid (mRNA) expression in cancerous tissues was measured by quantitative reverse transcription polymerase chain reaction. The correlation between the EGF SNP genotype and prognosis was statistically analyzed in the patients with HCC.ResultsThe proportion of the A/A, A/G, and G/G genotypes were 5.3%, 42.8%, and 51.9%, respectively, in the patients with HCC, whereas in those without HCC, they were 8.6%, 35.9%, and 55.5%, respectively, revealing that the odds ratio (OR) of developing HCC was higher in patients with a G allele (OR =1.94, P=0.080 for A/G patients and OR =1.52, P=0.261 for G/G patients, as compared with A/A patients). In particular, when the analysis was limited to the 363 patients with hepatitis C, the OR for developing HCC was 3.54 (P=0.014) for A/G patients and was 2.85 (P=0.042) for G/G patients, as compared with A/A patients. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.033). No statistically significant differences were observed between the EGF SNP genotype and diseasefree or overall survival.ConclusionThe EGF SNP genotype might be associated with a risk for the development of HCC in Japanese patients but not with prognosis. Of note, the association is significantly stronger in patients with hepatitis C, which is the main risk factor for HCC in Japan.

Epidermal Growth Factor Gene Polymorphism in Egyptian Patients with Hepatocellular carcinoma related to Hepatitis C

“…The G allele (A/G and G/G) had higher risk for developing HCC especially in HCV patients when compared with A/A patients. 20 But they could not explain why HCC was higher in patients with A/G genotype when compared with the G/G genotype; however, this has been observed occasionally, in other studies [13,21,22] .…”

Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: A systematic review

“…The EGF gene encodes epidermal growth factor. All studies found a significant association with the outcome, although for one, the association was only significant for the A/A to A/G comparison (and not for A/A to G/G). Additionally, a meta‐analysis describing comparisons between HCC patients and both patients with liver disease and healthy controls found a significant overall effect.…”

“…Three original studies were identified investigating the rs4444903 SNP of the EGF gene, two studying HCC(578 patients in total) and one studying fibrosis, with a variety of comparison groups (including HCV‐infected and HCV‐related cirrhosis patients). The EGF gene encodes epidermal growth factor.…”

CD44 single nucleotide polymorphism and isoform switching may predict gastric cancer recurrence

“…Many studies including meta-analyses have shown relationships between SNPs and human cancer susceptibility [21][22][23][24][25]. For these SNPs to be useful biomarkers, they should be validated in several populations because of racial differences [26]. However, the clinical significance of CD44 SNPs has not been thoroughly established, especially in patients with gastric cancer [8,11,[27][28][29][30][31][32].…”