Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: two case-control studies

Abstract

BackgroundEarlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk.MethodsThe EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China.ResultsFollowing adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93–12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China.ConclusionGenetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.

Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development

“…We observed that the IFN-γ level is decreased and the IL-4 level is increased in the serum of HCC patients compared to healthy controls, in agreement with a previous study (36). Cytokine profiles indicating a deregulation of both Th1-and Th2-type cells have been previously associated with the development of HCC (18).…”

In vitro differentiated hepatic oval‐like cells enhance hepatic regeneration in CCl4‐induced hepatic injury

“…Improvement of hepatic microenvironment by virtue of increased BM-OCs homing augments the hepatic markers expression in injured liver tissue (Figure 4). Previous studies demonstrated BMSCs differentiation toward hepatic lineage when transplanted (S anchez-Valle et al, 2012;Yuan et al, 2013) and these cells expressed hepatic markers in vivo (Ali and Masoud, 2012). Earlier, hepatic stem cells transplanted into rats with thioacetamide (TAA)-induced fibrosis effectively repopulate the liver with advanced fibrosis (Yovchev et al, 2014).…”

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

“…Overall, 2,095 patients with HCC and 3,766 control individuals were retrieved. Seven of the studies enrolled Chinese individuals (15,(22)(23)(24)(25)(26), three studies involved a mixed population, including Caucasian, Hispanic and Asian populations and individuals of African descent (21,22,27), one study enrolled only Caucasians (21) and one enrolled only Egyptian individuals (28). The genotype distributions in the controls for all studies were consistent with the HWE expectations.…”

“…The combined search yielded 132 studies, 123 of which were excluded as they clearly did not satisfy the inclusion criteria or were overlapping references (two or more publications from the same institute or duplicate publication using different languages). The publications by Zhong et al (15), Tanabe et al (21) and Yuan et al (22) all involved two independent case-control studies and were overall considered to be six single studies. Finally, a total of 12 studies (15,(21)(22)(23)(24)(25)(26)(27)(28) that examined the association between the EGF 61A/G polymorphism and the risk of HCC were included in the current meta-analysis (Fig.…”