Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population

Abstract

RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP-and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/ extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81∼2.61, p=0.01∼0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79 ∼2.78, p=0.01∼0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/-or ht1 -/-(HR=0.42∼0.66, p=0.006∼0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

Association Analysis of SERPINB5 Polymorphisms with HBV Clearance and HCC Occurrence in a Korean Population

“…This cycle of constant damaging and repair can lead to mistakes which may then result in carcinogenesis. Recently, it has been suggested that genetic polymorphisms may be associated with the risk of HCC (Chun et al, 2009;Kim et al, 2006;Oh et al, 2008;Park et al, 2006;Park et al, 2007;Shin et al, 2003;Shin et al, 2007).…”