Abstract 3145: Investigation of a functional polymorphism in the epidermal growth factor gene for pathogenesis and prognosis of hepatocellular carcinoma in Japanese patients.
Authors: Suenaga Masaya , Yamada Suguru , Fujii Tsutomu , Fuchs Bryan C. , Okumura Norio , Nakayama Goro , Takeda Shin , Tanabe Kenneth K. , Kodera Yasuhiro 
Published: August 2014

Abstract
[Introduction] A single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been investigated as a predictor of hepatocellular carcinoma (HCC). Previous reports identified an A to G transition at position 61 in the 5’ untranslated region of the EGF gene and demonstrated that the G/G genotype was associated with an increased risk of developing HCC as compared to the A/G and A/A genotype. Racial differences with respect to the distribution of this SNP have been reported; however, no investigation has examined a Japanese population.
[Objectives] To examine the relationship between EGF SNP genotype and the development and prognosis of HCC in a Japanese population.[Methods] Restriction fragment-length polymorphism was used to determine EGF SNP genotype in two hundred and eight patients with HCC, who underwent resection in our department between 1994 and 2010. The level of EGF mRNA expression in cancerous tissues was measured by quantitative reverse transcription-PCR. EGF SNP was also analyzed in three hundred and four patients with either hepatitis, liver cirrhosis, or healthy controls. The correlation between EGF SNP genotype and prognosis was statistically analyzed in patients with HCC.
[Results] A/A, A/G, and G/G genotype were 5.3%, 42.8%, and 51.9% in the Japanese patients with HCC. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.04). A/A, A/G, and G/G genotype were 8.2%, 35.9%, and 55.9% in patients without HCC. Analysis of the distribution of allelic frequencies revealed that the odds ratios of developing HCC were 1.86 (95% CI 0.88-4.12, P=0.23) in A/G patients and 1.44 (95% CI 0.70-3.17, P=0.33) in G/G patients compared with A/A patients. However, when the analysis was limited to patients with hepatitis C, the odds ratio were 3.37 (95% CI 1.20-12.06, P=0.02) in A/G patients, and 2.77 (95% CI 1.10-9.78, P=0.04) in G/G patients, compared with A/A patients. 3) No statistically significant differences were observed between EGF SNP genotype and disease-free and overall survival.
[Conclusions] The frequency of the EGF SNP genotype in a Japanese population was characterized by a very low distribution of A/A patients. The EGF 61*G allele was associated with greater EGF mRNA expression in HCC tissue. The EGF SNP genotype was also associated with risk for development of HCC in hepatitis C patients but not with prognosis.
Citation Format: Masaya Suenaga, Suguru Yamada, Tsutomu Fujii, Bryan C. Fuchs, Norio Okumura, Goro Nakayama, Shin Takeda, Kenneth K. Tanabe, Yasuhiro Kodera. Investigation of a functional polymorphism in the epidermal growth factor gene for pathogenesis and prognosis of hepatocellular carcinoma in Japanese patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3145. doi:10.1158/1538-7445.AM2013-3145