Role of EGF Gene Functional Polymorphism in the Developmentf Hepatocellular Carcinoma among Hepatitis B Carriers
Date Issued
2009
Date
2009
Author(s)
Chen, Li-Ying
Abstract
Background: The epidermal growth factor (EGF) signaling pathway affects cell proliferation and differentiation. Polymorphism in the EGF gene may play a role in theevelopment of epithelial cancers, such as hepatocellular carcinoma (HCC). Methods: We genotyped two EGF functional polymorphisms (rs4444903 at 5’ untranslated regionUTR] and rs11569017 at exon 15) in a cohort of 4432 cancer-free HBsAg-positive men (of whom 200 developed HCC and 4232 remained unaffected through 16 years ofollow-up) who were recruited from Government Employee Central Clinics and Chang Gung Memorial Hospital between 1989 and 1992. To evaluate the impact of HBV viralactors on the association between the EGF SNPs and HCC, a longitudinal viral-load study (n=1133) with available data on HBeAg status and HBV genotype and DNA were also conducted within the cohort study. Results: We did not observe any association with the two EGF SNPs for HCC or cirrhosis. However, a statistically, significantly inverse association was found between SNP rs4444903 and circulating HBV DNA level, irrespective of cross-sectional (adjusted odds ratio [95% confidence interval]: AG vsA= 0.56 [95% CI=0.35-0.91]; GG vs AA= 0.54 [95% CI=0.33-0.86]) or longitudinal (adjusted odds ratio [95% confidence interval]: AG vs AA= 0.68 [95% CI=0.56-0.83];G vs AA= 0.67 [95% CI=0.56-0.82]) measure of viral load. Conclusion: Our results argue against a role of the EGF 5’ UTR SNP in epithelial cancers. EGF geneticolymorphism may alter viral replication activity during the development of HCC among HBsAg carriers. A better understanding of the relationship between the EGF 5’TR SNP and viral load might be valuable for monitoring HBsAg carriers with HCC under treatment with inhibitors of EGF signaling pathway.
Subjects
Epidermal growth factor
Gene polymorphism
Hepatitis B virus
Hepatocellular carcinoma
Cohort study
SDGs
Type
thesis
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