• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2517-2522
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• 2014

Background: Several recent studies have explored associations between pre-mir-218 polymorphism (rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimation of the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials and Methods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China National Knowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies were analyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs) and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showed that the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versus AA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96), and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models (GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significant association between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in all comparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10; GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: The findings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development in Chinese. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions.

• Korean Journal of Radiology
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• v.24 no.8
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• pp.761-771
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• 2023

Objective: To investigate the association among the electrode placement method, electrode type, and local tumor progression (LTP) following percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) and to assess the risk factors for LTP. Materials and Methods: In this retrospective study, we enrolled 211 patients, including 150 males and 61 females, who had undergone ultrasound-guided RFA for a single HCC < 3 cm. Patients were divided into four combination groups of the electrode type and placement method: 1) tumor-puncturing with an internally cooled tip (ICT), 2) tumor-puncturing with an internally cooled wet tip (ICWT), 3) no-touch with ICT, and 4) no-touch with ICWT. Univariable and multivariable Cox proportional-hazards regression analyses were performed to evaluate the risk factors for LTP. The major RFA-related complications were assessed. Results: Overall, 83, 34, 80, and 14 patients were included in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. The cumulative LTP rates differed significantly among the four groups. Compared to tumor puncturing with ICT, tumor puncturing with ICWT was associated with a lower LTP risk (adjusted hazard ratio [aHR] = 0.11, 95% confidence interval [CI] = 0-0.88, P = 0.034). However, the cumulative LTP rate did not differ significantly between tumor-puncturing with ICT and no-touch RFA with ICT (aHR = 0.34, 95% CI = 0.03-1.62, P = 0.188) or ICWT (aHR = 0.28, 95% CI = 0-2.28, P = 0.294). An insufficient ablative margin was a risk factor for LTP (aHR = 6.13, 95% CI = 1.41-22.49, P = 0.019). The major complication rates were 1.2%, 0%, 2.5%, and 21.4% in the ICT, ICWT, no-touch with ICT, and no-touch with ICWT groups, respectively. Conclusion: ICWT was associated with a lower LTP rate compared to ICT when performing tumor-puncturing RFA. An insufficient ablation margin was a risk factor for LTP.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1043-1047
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• 2013

Although there have been many studies investigating possible associations between the C1653T mutation and risk of HCC, the results have been inconsistent. We conducted searches of the published literature in Pubmed and Embase databases up to January 2013. Seventeen studies with a total of 1,085 HCC cases and 1,365 healthy controls were retrieved. We found a significant association between the C1653T mutation and HCC risk (OR = 2.01, 95%CI= 1.49-2.70). In the subgroup analysis by ethnicity, a significant association was also found in Asians (OR = 2.07, 95%CI= 1.71-2.51). In subgroup analysis by HBV genotype, B and C were linked with development of HCC (B:OR = 2.21, 95%CI= 1.13-4.34; C:OR = 2.26, 95%CI= 1.61-3.16). However, no significant association was found between the C1653T mutation and HCC risk in HBeAg positive cases. In conclusion, this meta-analysis suggests that the C1653T mutation may be associated with susceptibility to HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• Genomics & Informatics
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• v.6 no.4
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• pp.181-191
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• 2008

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${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5069-5073
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• 2015

The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2979-2986
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• 2014

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5761-5767
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• 2013

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3253-3256
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• 2015

Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1657-1663
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• 2015

Background: Early diagnosis of hepatocellular carcinoma (HCC) is the most important step in successful treatment. However, it is usually rare due to the lack of a highly sensitive specific biomarker so that the HCC is usually fatal within few months after diagnosis. The aim of this work was to study the role of plasma nuclear factor kappa B (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) as diagnostic biomarkers for early detection of HCC in a high-risk population. Materials and Methods: Plasma nuclear factor kappa B level (NF-${\kappa}B$) and serum peroxiredoxin 3 (PRDX3) levels were measured using enzyme linked immunosorbent assay (ELISA), in addition to alpha-fetoprotein (AFP) in 72 cirrhotic patients, 64 patients with HCC and 29 healthy controls. Results: NF-${\kappa}B$ and PRDX3 were significantly elevated in the HCC group in relation to the others. Higher area under curve (AUC) of 0.854 (for PRDX3) and 0.825 (for NF-${\kappa}B$) with sensitivity of 86.3% and 84.4% and specificity of 75.8% and 75.4% respectively, were found compared to AUC of alpha-fetoprotein (AFP) (0.65) with sensitivity of 72.4% and specificity of 64.3%. Conclusions: NF-${\kappa}B$ and PRDX3 may serve as early and sensitive biomarkers for early detection of HCC facilitating improved management. The role of nuclear factor kappa B (NF-${\kappa}B$) as a target for treatment of liver fibrosis and HCC must be widely evaluated.