• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1769-1772
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• 2013

A case-control study of the association of miR-499A>G rs3746444 with risk of hepatocellular carcinoma (HCC)was conducted. Patients with HCC and healthy control subjects were recruited for genotyping of miR-499A>G using duplex polymerase-chain-reaction with confronting-two-pair primer(PCR-RFLP) analysis. The MiR-499 GG genotype was associated with a decreased risk of HCC as compared with the miR-499 AA genotype (adjusted OR=0.74, 95%CI=0.24-0.96). Similarly, the GG genotype showed a 0.45-fold decreased HCC risk in a recessive model. The MiR-499 G allele was significantly associated with decreased risk of HCC among patients infected with HBV in a dominant model (OR=0.09, 95%CI= 0.02-0.29). In conclusion, the MiR-499A>G rs3746444 polymorphism is associated with HCC risk in the Chinese population, and may be useful predictive marker for CAD susceptibility.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4423-4426
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• 2012

Aim: XRCC1 and XPD are two major repair genes involved in nucleotide excision repair (NER), which is reported to be associated with risk of several cancers. We explored the association of XRCC1 and XPD polymorphisms with the risk of HCC. Methods: A total of 410 cases with HCC and 410 health controls were collected. XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn genotyping was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer (PCR-CTPP) method. Results: XRCC1 194Trp/Trp was strongly significantly associated with an increased risk of HCC cancer when compared with the wide-type genotype (OR=2.26, 95% CI=(1.23-5.38). Individuals carrying the XRCC1 399Gln/Gln showed increased risk of HCC (OR=1.74, 95%CI=1.06-2.74). The XPD 751Gln/Gln and Gln allele genotype were associated with strong elevated susceptibility to HCC (OR=3.51 and 1.42, respectively). Conclusion: These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in risk of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6601-6604
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• 2013

Aim: Associations between polymorphisms in miR-146aG>C, miR-196a2C>T and miR-499A>G and risk of HCC, and interaction with HBV infection in a Chinese population, were the target of the present research. Methods: The duplex polymerase-chain-reaction with confronting-two-pair primers (PCR-RFLP) was performed to determine the genotypes of the miR-146aG>C, miR-196a2C>T and miR-499A>G genotypes. Associations of polymorphisms with the risk of HCC were estimated by conditional logistic regression analysis. Results: Drinking, family history of cancer, HBsAg and HCV were risk factors for HCC. Multivariate regression analyses showed that subjects carrying the miR-196a2 CC genotype had significantly increased risk of HCC, with an adjusted OR (95% CI) of 2.18 (1.23-3.80). In addition, cases carrying the miR-196a2 C allele had a 1.64-fold increase in the risk for HCC (95%CI=1.03-2.49). The miR-196a2 CT and TT genotypes greatly significantly increased the risk of HCC in subjects with HBV infection, with adjusted ORs (95% CI) of 2.02 (1.12-3.68) and 2.69 (1.28-5.71), respectively. Conclusion: Our results demonstrate that miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese, especially in patients with HBV infection.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4305-4309
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• 2012

Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6961-6967
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• 2014

Cytokine gene single nucleotide polymorphisms (SNPs) are involved in the genesis and progression of hepatocellular carcinoma (HCC). We hypothesized that combined effects of cytokine gene SNPs and SNP-SNP interactions are associated with HCC risk. Six SNPs in cytokine genes (IL-2, IFN-${\gamma}$, IL-$1{\beta}$, IL-6, and IL-10) were genotyped in a study of 720 Chinese HCC cases and 784 cancer-free controls. Although none of these SNPs individually had a significant effect on the risk of HCC, we found that the combined effects of these six SNPs may contribute to HCC risk (OR=1.821, 95% CI=1.078-3.075). This risk was pronounced among smokers, drinkers, and hepatitis B virus carriers. A SNP-SNP interaction between IL-2-330 and IFN-${\gamma}$-1615 was associated with an increased HCC risk (OR=1.078, 95% CI=1.022-1.136). In conclusion, combined effects of SNPs and SNP-SNP interactions in cytokine genes may contribute to HCC risk.

• 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.13
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• pp.5343-5348
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• 2015

Promoter hypermethylation of the runt-related transcription factor 3 (RUNX3) gene is associated with increased risk of hepatocellular carcinoma (HCC). Oxidative stress plays a vital role in both carcinogenesis and progression of HCC. However, whether oxidative stress and RUNX3 hypermethylation in HCC have a cause-and-effect relationship is not known. In this study, plasma protein carbonyl and total antioxidant capacity (TAC) in patients with hepatitis B virus (HBV)-associated HCC (n=60) and age-matched healthy subjects (n=80) was determined. RUNX3 methylation in peripheral blood mononuclear cells (PBMC) of subjects was measured by methylation-specific PCR. Effect of reactive oxygen species (ROS) on induction of RUNX3 hypermethylation in HCC cells was investigated. Plasma protein carbonyl content was significantly higher, whereas plasma TAC was significantly lower, in HCC patients than healthy controls. Based on logistic regression, increased plasma protein carbonyl and decreased plasma TAC were independently associated with increased risk for HCC. PBMC RUNX3 methylation in the patient group was significantly greater than in the healthy group. RUNX3 methylation in hydrogen peroxide ($H_2O_2$)-treated HepG2 cells was significantly higher than in untreated control cells. In conclusion, increase in oxidative stress in Thai patients with HBV-associated HCC was demonstrated. This oxidative increment was independently associated with an increased risk for HCC development. RUNX3 in PBMC was found to be hypermethylated in the HCC patients. In vitro, RUNX3 hypermethylation was experimentally induced by $H_2O_2$. Our findings suggest that oxidative stress is a cause of RUNX3 promoter hypermethylation in HCC cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7139-7142
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• 2015

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7331-7333
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• 2013

Aim: To investigate associations of fasting insulin and glucose levels in serum with hepatocellular carcinoma risk. Materials and Methods: This hospital based study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalese Army Institute of Health Sciences, between 1st December, 2011 and 31st June, 2013. The variables collected were age, fasting plasma glucose, fasting plasma insulin and ALT. Quantitative determination of human insulin concentrations was accomplished by chemiluminescence enzyme immunoassay. Results: Of the total 220 subjects enrolled in our present study, 20 cases were of HCC and 200 were healthy controls. The maximum number of cases of hepatocellular carcinoma in category cutpoints of fasting insulin levels fell in the range of >6.10 ${\mu}U/ml$. The highest insulin levels (>6.10 ${\mu}U/ml$) were seen to be associated with an 2.36 fold risk of HCC when compared with fasting insulin levels of (<2.75 ${\mu}U/ml$). Furthermore, the insulin levels (2.75-4.10 ${\mu}U/ml$) of category cutpoints also conferred a 1.57 fold risk for HCC when compared with lowest fasting insulin levels of (<2.75 ${\mu}U/ml$). Conclusions: The effect of an insulin level in increasing HCC risk appeared consistent, influencing incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6591-6596
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• 2014

Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.