• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.191-194
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• 2012

We conducted a case-control study in China to clarify the association between XRCC1-Arg399Gln polymorphism and HCC risk. A total of 150 cases and 158 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reaction with the confronting-two-pairprimer (PCR-CTPP) method. All analyses were performed using the STATA statistical package. A significantly increased risk was associated with the Arg/Gln genotype (adjusted OR 1.78, 95%CI=1.13-2.79) compared with genotype Arg/Arg. In contrast, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.69 (0.93-2.66). A significant association was found between positive HBsAg and Arg/Gln, with an OR of 3.43 (95% CI=1.45-8.13). Patients carrying Gln/Gln genotypes showed significantly lower median survival than Arg/Arg genotypes (HR=1.38, 95% CI=1.04-1.84). Further Kaplan-Meier analysis showed decreased median survival in Arg/Gln+Gln/Gln genotype carriers in comparison to Arg/Arg carriers (HR=1.33, 95% CI=1.02-1.76). In conclusion, we observed that XRCC1-Arg399Cln polymorphism is associated with susceptibility to HCC, and XRCC1 Gln allele genotype showed significant prognostic associations.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8197-8201
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• 2014

Background: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). Materials and Methods: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. Results: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). Conclusions: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3247-3252
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• 2012

Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome. Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected from May 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1 IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who received chemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This study indicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6673-6678
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• 2014

Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Materials and Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. Results: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including ${\alpha}$-fetoprotein ${\leq}400ng/mL$ (45.4% vs 16.7%; p=0.006), tumor size ${\leq}5cm$ (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Conclusions: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7101-7106
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• 2013

Background: The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ${\leq}$ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. Methods: A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. Results: After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ${\leq}$ 1-year) of HCC meeting Milan criteria. Conclusions: AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

• 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.

• Korean Journal of Clinical Laboratory Science
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• v.43 no.4
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• pp.150-155
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• 2011

It is a very important diagnosis and evalution of Hepatocellular carcinoma (HCC) in Korea where hepatitis B-virus is endemic. Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker. This study was purposed to investigate usefulness of PIVKA-II in the diagnosis and fallow-up after treatment of HCC. A total of 418 patients were included in 187 patients (44.7%) of HCC, 83 patients (19.9%) of liver cirrhosis, 74 patients (17.7%) of chronic hepatitis and 74 patients (17.7%) of other liver diseases with serum PIVKA-II levels by Hicatch PIVKA-II kit. PIVKA-II level were analysed for difference of groups and the comparison of treatment responses. The sensitivity and specificity of PIVKA-II in the diagnosis of HCC were 80.2%, 87.0% at the cut-off value of 40 mAU/mL. There were statistically significant difference between the HCC and other groups (p<0.001), before and after PIVKA-II levels after treatment in HCC (p<0.001). PIVKA-II can be used as a useful tumor marker for patients with HCC, especially early diagnosis in high risk groups, treatment response assesment and monitoring of recurrence.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.36-41
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• 2015

Purpose: To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Materials and Methods: Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Results: Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. Conclusion: WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7441-7447
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• 2015

Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6457-6461
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• 2015

MicroRNAs directly and indirectly influence many biological processes such as apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and metastasis. They modulate gene expression at the posttranscriptional level and are associated with progression of liver disease. Hepatocellular carcinoma (HCC) is a cancer which mostly occurs in males. There are many factors affect HCC development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), co-infection, environmental factors including alcohol, aflatoxin consumption and host-related factors such as age, gender immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic infection with the hepatitis B virus is the major factor leading to HCC progression since it causes the liver injury. At present, there are many reports regarding the association of SNPs on miRNAs and the HCC progression. In this research, we investigated the role of miR-149 (rs2292832) and miR-101-1 (rs7536540) with HCC progression in Thai population. The study included 289 Thai subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus infection (CHB) and 95 healthy control subjects. The allele and genotype of rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR assay. Our results revealed no significant association between miR-149 (rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population. However, this research is the first study of miR-149 (rs2292832) and miR-101-1 (rs7536540) in HCC in Thai populations and the results need to be confirmed with a larger population.