• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4759-4763
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• 2013

Background: Prognostic factors of postoperative early and late recurrence in patients with hepatocellular carcinoma (HCC) undergoing curative resection remain to be clarified. The aim of this study was to identify risk factors for postoperative early (${\leq}$ 2 year) and late (> 2 year) intrahepatic recurrences in patients with single HCCs without macrovascular invasion. Methods: A total of 280 patients from December 2004 to December 2007 were retrospectively included in this study. Intrahepatic recurrence was classified into early (${\leq}$ 2 year) and late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate logistic regression analysis were performed to determine significant risk factors. Results: During the follow-up, 124 patients had intrahepatic recurrence, early and late in 82 and 42 patients, respectively. Multivariate logistic regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95% CI: 1.290-4.451) was the only independent risk factor for early recurrence, while being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent risk factors for late recurrence. Conclusions: Early and late recurrence of HCC is linked to different risk factors in patients with single HCC without macrovascular invasion. This results suggested different emphases of strategies for prevent of recurrence after curative resection, more active intervention including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being necessary for patients with relevant risk factors.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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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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• 제14권1호
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• pp.355-358
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• 2013

XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.

• 응용통계연구
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• 제15권1호
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• pp.1-8
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• 2002

예후인자의 범주화는 질병의 진단, 치료법 결정 및 임상시험의 참여기준 설정 등에 매우 유용하다. 예후인자의 범주화 방법으로는 생물학적 이론에 따라 경계값을 정하는 방법, 자료의 그래프를 이용하는 방법, 모든 가능한 경계 값들을 적용해보는 최소 유의확률 방법 등이 있다. 또한 최소 유의확률 방법의 다중검정문제를 보완한 몇 가지 방법들이 있다. 본 연구에서는 우리 나라에서 높은 발생률을 보이는 간세포암종의 절제술을 받은 환자들에 있어서 간 절제술 후 재발위험이 높은 군을 구별하는 한 근거로 종양의 크기를 범주화하기 위한 경계값을 결정하고자 하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2429-2434
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• 2016

Transforming growth factor-B1 ($TGF-{\beta}1$ )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of $ENG/TGF-{\beta}1$ mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and $TGF-{\beta}1$mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of $TGF-{\beta}1$mRNA was 1.4 (0.19 -6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and $TGF-{\beta}1$ mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (P<0.05). Our data suggested that increased ENG and $TGF-{\beta}1$ gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and $TGF-{\beta}1$ as targets for therapy and treatment strategies are warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2771-2775
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• 2015

Background: Associations between ABO blood groups and risk of several malignancies have been reported, although there are limited data regarding hepatocellular carcinoma (HCC). The aim of this study was to investigate any possible association between the ABO genotype, especially blood group A, and HCC risk in Koreans. Materials and Methods: We conducted a case-control study of 1,538 patients with newly diagnosed HCC at Chonnam National University Hwasun Hospital and 1,305 randomly selected members of the general population. The ABO genotype was determined by multicolor real-time polymerase chain reaction (PCR) using displacing probes. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) were calculated using logistic regression models with adjustment for gender, age, smoking, alcohol drinking, and hepatitis B and C status. Results: The risk of HCC in genotype AA was significantly higher than in OO (aOR=1.773, 95% CI=1.161-2.705). The risk in blood group A was also higher than in blood group O (aOR=1.448, 95% CI=1.005 1.897). No significant difference was found for the AA, BO, BB, and AB genotypes, or blood group B and AB. Conclusions: Blood group A and genotype AA showed the highest risks of HCC in a Korean population. No significant difference was found for the AO, BO, BB, and AB genotypes, or blood group B and AB.

• Genomics & Informatics
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• 제6권4호
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• pp.192-201
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• 2008

Erythropoietin-producing human hepatocellular carcinoma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular system development. Eph receptor overexpression has been observed in various cancers and is related to the malignant transformation, metastasis, and differentiation of cancers, including hepatocellular carcinoma (HCC). Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. EphrinB1, the ligand of EPHB1, has been shown to regulate HCC carcinogenesis. Here, we sought to determine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, including chronic liver disease (CLD) and HCC. We genotyped 26 EPHB1 single nucleotide polymorphisms (SNPs) in 399 Korean CLD, HCC, and LD (CLD+HCC) cases and seroconverted controls (HBV clearance, CLE) using the GoldenGate assay. Two SNPs (rs6793828 and rs11717042) and 1 haplotype that were composed of these SNPs were associated with an increased risk for CLD, HCC, and LD (CLD+HCC) compared with CLE. Haplotypes that could be associated with HBV-infected liver diseases by affecting downstream signaling were located in the Eph tyrosine kinase domain of EPHB1. Therefore, we suggest that EPHB1 SNPs, haplotypes, and diplotypes may be genetic markers for the progression of HBV-associated acute hepatitis to CLD and HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4851-4856
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• 2014

Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTMl null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Metbods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

• 대한유전성대사질환학회지
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• 제13권1호
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• pp.48-53
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• 2013

Tyrosinemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma in childhood or early adolescence. We studied a 37-year-old woman with tyrosinemia I whose severe liver disease in infancy and rickets during childhood were resolved with dietary therapy. From 14 years of age, she resumed unrestricted diet with the continued presence of the biochemical features of tyrosinemia, yet maintained normal liver function. In adult years, she accumulated only a small amount of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1G>T, and a novel missense mutation, p.Q279R. Studies of resected liver revealed the absence of hydrolytic activity and immunological expression of fumarylacetoacetate hydrolase in tumour. In the non-tumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase were found. This case demonstrates the high risk of liver cancer in tyrosinemia I even in a seemingly favorable biological environment. In this study of tyrosinemia I, Case 2 with negative succinylacetone accumulation and the recovery of acute liver failure was compared with Case 1. Diet restriction and NTBC treatment are crucial to prevent hepatocellular carcinoma until liver transplant can take place and cure the condition. Further studies are needed to examine cases where liver cancer did not result despite clinical symptoms/signs of tyrosinemia type I.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3009-3014
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• 2015

The epidermal growth factor (EGF) may play a pathological role in hepatocellular carcinoma (HCC). However, the conclusions of published reports on the relationship between the EGF $61^*A/G$ polymorphism and HCC risk remain controversial. To derive a more precise estimation we performed a meta-analysis based on 14 studies that together included 2,506 cases and 4,386 controls. PubMed, EMBASE, Web of Knowledge and the Chinese National Knowledge Infrastructure (CNKI) databases were used to retrieve articles up to August 1, 2014. The crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the association. Meta-analysis results showed a significant association between the EGF $61^*A/G$ polymorphism and HCC risk in all four genetic models (allele model: OR=1.25, 95%CI=1.12-1.40; dominant model: OR=1.32, 95%CI=1.14-1.54; recessive model: OR=1.33, 95%CI=1.12-1.58; ho-mozygous model: OR=1.59, 95%CI=1.33-1.90). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology and genotype methods. Thus, this meta-analysis suggests that the G-allele of the EGF $61^*A/G$ polymorphism is associated with an increased risk of HCC, especially in Asians and Caucasians, without influence from the source of controls or etiological diversity. Further studies with larger population sizes are needed to confirm these results.