Hepatocellular Carcinoma In Chinese Research Articles

Association of cytotoxic T-lymphocyte antigen-4 + 49A/G gene polymorphism with hepatocellular carcinoma risk in Chinese.

Hepatocellular carcinoma (HCC), a common cause of cancer-associated mortalities worldwide, is a complex polygenic disease, and its development is dependent on many genetic factors. Hepatitis B virus infection, also called chronic hepatitis B (CHB), is the leading cause of HCC. This meta-analysis was performed to assess the association between cytotoxic T-lymphocyte antigen-4 (CTLA4) +49A/G and HCC risk. The association studies were recruited from PubMed and China Biological Medicine Database, and eligible studies were included and synthesized using meta-analysis method. Four reports were included into this meta-analysis for the association of CTLA4 A/G gene polymorphism and HCC risk, and all the included studies were from Chinese. The association between CTLA4 A/G gene polymorphism and HCC risk was found in this meta-analysis (G allele: odds ratio [OR] =1.21, 95% confidence interval [CI]: 1.03-1.44, P = 0.02; GG genotype: OR = 1.21, 95% CI: 1.03-1.44, P = 0.02; AA genotype: OR = 1.37, 95% CI: 1.10-1.69, P = 0.004). Furthermore, G allele and GG genotype were associated with the CHB patients developing into HCC (G allele: OR = 0.81, 95% CI: 0.66-0.98, P = 0.03; GG genotype: OR = 0.75, 95% CI: 0.57-0.99, P = 0.04). CTLA4 A/G gene polymorphism was associated with HCC risk and CTLA4 G allele/GG genotype is associated with CHB patients developing into HCC in Chinese.

Association of the GLB1 rs4678680 genetic variant with risk of HBV-related hepatocellular carcinoma.

Accumulated evidences demonstrated that GLB1 is involved in cell senescence and cancer development. The GLB1 rs4678680 single nucleotide polymorphism (SNP) has been identified as a hepatocellular carcinoma (HCC) susceptibility polymorphism by a genome-wide association study in Korean population previously. However, little or nothing was known about its involvement and functional significance in hepatitis B viruses (HBV)-related HCC in Chinese. Therefore, we investigated the association between the GLB1 rs4678680 SNP and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two medical centers of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The potential regulation role the rs4678680 genetic variant on GLB1 expression was examined with HCC and normal liver tissues. We found that The rs4678680 G allele was showed to be risk allele; individuals with the TG genotype had an OR of 1.51 (95% CI = 1.10–2.07, P = 0.010, Shandong set) or 1.49 (95% CI = 1.11–1.99, P = 0.008, Jiangsu set) for developing HBV-related HCC, respectively, compared with individuals with the TT genotype. This association was more pronounced in males, individuals aged older than 57 years and drinkers (all P < 0.05). In the genotype-phenotype correlation analyses of fifty-six human liver tissue samples, rs4678680 TG or GG was associated with a statistically significant increase of GLB1 mRNA expression (P < 0.05). Our data indicated that the GLB1 rs4678680 SNP contributes to susceptibility to develop HBV-related HCC, highlighting the involvement of GLB1 and cell senescence in etiology of HCC.

A genetic variant at KIF1B predicts clinical outcome of HBV-related hepatocellular carcinoma in Chinese

BackgroundRecently, a genome-wide association study conducted in Chinese reported a single nucleotide polymorphism at KIF1B, rs17401966, associated with the susceptibility of hepatitis B virus-related hepatocellular carcinoma. In this study, we aim to investigate the effect of rs17401966 on the prognosis of hepatitis B virus-related hepatocellular carcinoma patients at intermediate or advanced stages. MethodsThe SNP rs17401966 was genotyped using the TaqMan allelic discrimination assay in 414 intermediate or advanced hepatocellular carcinoma patients. Log-rank test and Cox proportional hazard models were used for survival analyses. ResultsPrevious studies have identified that the G allele of rs17401966 demonstrated protective effect for the susceptibility of hepatitis B virus-related hepatocellular carcinoma. Here we found that subjects carrying the G allele of rs17401966 was significantly associated with a better survival compared with those carrying the A allele (adjusted hazard ratio=0.82, 95% confidence intervals=0.68–0.99, P=0.044 in an additive genetic model). ConclusionThe variant G allele of rs17401966 may be a favorable biomarker for the prognosis of intermediate or advanced hepatitis B virus-related hepatocellular carcinoma patients in this Chinese population.

A Genetic Variant in the Promoter Region of miR-106b-25 Cluster Predict Clinical Outcome of HBV-Related Hepatocellular Carcinoma in Chinese

Background MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.MethodsThe SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis.ResultsThe variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) = 0.76,95% confidence intervals (CI) = 0.59–0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR = 0.72, 95% CI = 0.56–0.91, P = 0.007).ConclusionsThese findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.

A 3′ UTR SNP in COL18A1 Is Associated with Susceptibility to HBV Related Hepatocellular Carcinoma in Chinese: Three Independent Case-Control Studies

BackgroundAccumulated evidences indicate that single nucleotide polymorphisms (SNP) in angiogenesis and tumorigenesis related genes are associated with risk of Hepatocellular carcinoma (HCC). COL18A1 encodes the precursor of endostatin, which is a broad-spectrum angiogenesis inhibitor, and we speculate that SNPs in COL18A1 may be associated with susceptibility to HCC.Methods and FindingsWe carried out a 2-stage association study in 3 independent case-control groups in a total of 1067 chronic hepatitis B (CHB) patients and 808 hepatitis B virus (HBV) related HCC patients in Han Chinese. Four SNPs which can represent all potential functional SNPs with MAF>0.1 recorded in HapMap database were genotyped using TaqMan methods. Levels of total COL18A1 mRNA were also examined using quantitative real-time RT-PCR. We found that rs7499 located in 3′-UTR to be strongly associated with HBV related HCC (Pcombined = 0.0000005, OR = 0.72, 95%CI = 0.63–0.82). COL18A1 mRNA expression was significantly decreased as the disease progressed (P = 0.000026).ConclusionThese findings indicate that COL18A1 rs7499 may contribute to the risk of HCC in Han Chinese.

Relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma

The purpose of this study was to discuss the relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma (HCC) in Chinese population. In this case-control study, 1300 cases of HBV positive patients were recruited in case group and another 1344 cases of persistent chronic HBV carriers were selected as control. 5 ml of blood sample was collected from each subject, from which the DNA was extracted; and rs10877887 and rs13293512 in promoter region let-7 were selected as the study sites. The polymorphism was detected by TaqMan allelic discrimination assay and the OR value (95%CI) was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to HCC and different genotypes. The frequencies of genotype TT, CT and CC in site rs10877887 were 43.0% (542/1261), 44.7% (564/1261) and 12.3% (155/1261) respectively in case group; while separately 44.0% (581/1319), 44.4% (585/1319) and 11.6% (153/1319)in control group. The frequencies of genotype TT, CT and CC in site rs13293512 were 32.0% (406/1270), 48.1% (611/1270) and 19.9% (253/1270) respectively in case group; while separately 33.1% (427/1291), 49.4% (638/1291) and 17.5% (226/1291) in control group. The results of multifactor logistic regression analysis showed no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs10877887 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.05, 95%CI: 0.90 - 1.23); and either no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs13293512 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.06, 95%CI: 0.89 - 1.25). The united-analysis of the two sites showed the frequencies of 0, 1, 2 and 3-4 mutated-genotype C were 13.3% (164/1235), 36.2% (447/1235), 33.0% (408/1235) and 17.5% (216/1235) respectively in case group; and separately 14.2% (181/1269), 37.0% (469/1269), 33.1% (420/1269) and 15.7% (199/1269) in control group. The susceptibility to HCC in 1,2,3-4 mutated-genotype C carriers were 1.05 (0.81 - 1.34), 1.07 (0.83 - 1.38) and 1.22 (0.91 - 1.62) times of the non-mutated genotype subjects; but there was no statistical significance (Wald χ(2) = 1.79, P = 0.181). The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.

Coffee consumption and reduced risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study

Coffee consumption has been associated with reduced markers of hepatic cell damage, reduced risk of chronic liver disease, and cirrhosis across a variety of populations. Data on the association between coffee consumption and risk of hepatocellular carcinoma (HCC), especially in high-risk populations, are sparse. This study examines the relationship between coffee and caffeine consumption, and the risk of developing HCC within the Singapore Chinese Health Study, a prospective cohort of 63,257 middle-aged and older Chinese men and women, a relatively high-risk population for HCC. Baseline data on coffee consumption and other dietary and lifestyle factors were collected through in-person interviews at enrollment between 1993 and 1998. As of 31 December 2006, 362 cohort participants had developed HCC. High levels of coffee or caffeine consumption were associated with reduced risk of HCC (p for trend < 0.05). Compared with non-drinkers of coffee, individuals who consumed three or more cups of coffee per day experienced a statistically significant 44% reduction in risk of HCC (hazard ratio 0.56, 95% confidence interval, 0.31-1.00, p = .049) after adjustment for potential confounders and tea consumption. These data suggest that coffee consumption may reduce the risk of developing HCC in Chinese in Singapore.

The Vascular Endothelial Growth Factor-2549 Insertion/Deletion Polymorphism Is Not Associated with Susceptibility to Hepatocellular Carcinoma in Chinese

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, which is crucial for development and metastasis of tumors including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. Polymorphisms in VEGF may alter VEGF protein concentrations, influence the process of angiogenesis, and may relate to interindividual variation in tumorigenesis. In this study, we carried out a case-control study in a Chinese population (206 cases and 302 controls) to estimate the susceptibility to HCC associated with an 18-bp insertion/deletion polymorphism (rs35569394) in the promoter region of VEGF. After adjusting the data by gender, age, smoking status, drinking status, and hepatitis B virus (HBV) infection using logistic regression model, we found that rs35569394 was not associated with HCC, at both the allele and genotype levels. Thus, rs35569394 should not be viewed as a major contributor to the development of HCC in Chinese.

An insertion/deletion polymorphism in the 3′ untranslated region of β-transducin repeat-containing protein (βTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFκB signaling pathway, β-transducin repeat-containing protein (βTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of βTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9bp insertion/deletion polymorphism (rs16405) in 3′ untranslated region of βTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR=0.44 (0.24–0.83) (p=0.004) and OR=0.56 (0.31–1.00) (p=0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of βTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of βTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which would negatively regulate βTrCP. We propose a microRNA-920 mediated βTrCP regulation model depending on rs16405 genotype, which warrants further replication association studies and follow-up functional experiments.

Association of polymorphisms of human leucocyte antigen‐DQA1 and DQB1 alleles with chronic hepatitis B virus infection, liver cirrhosis and hepatocellular carcinoma in Chinese

To investigate whether human leucocyte antigen (HLA) class II DQA1 and DQB1 gene polymorphisms are associated with chronic hepatitis B virus (HBV) infection and development of HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC), we detected the DQA1 and DQB1 allele polymorphisms in 168 HBV carriers (including 48 chronic hepatitis B, 42 LC and 78 HCC patients) and 100 controls who had recovered from HBV infection by using polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Our data suggest that DQA1*0102 and DQA1*0104 were associated with protection from chronic HBV infection (P(c) = 0.003) and development of LC (P(c) = 0.001), respectively, whereas DQB1*0201 conferred susceptible effect on chronic HBV infection (P(c) = 0.008). We also found that DQA1*0601, DQB1*0601 and DQA1*0201 showed some susceptible effect on chronic HBV infection and LC, respectively, however, these associations were no longer significant after Bonferroni correction (P(c) = 0.390, P(c) = 0.475 and P(c) = 0.140, respectively). No significant association has been found between DQA1 and DQB1 alleles and development of HCC. These results indicate that different subtypes of HLA-DQA1 and DQB1 are associated with development of chronic HBV infection and LC, respectively, in Han Chinese population.

Frequency and nature of cytokine gene polymorphisms in hepatocellular carcinoma in Hong Kong Chinese.

The genetic basis of susceptibility to hepatocellular carcinoma (HCC) is poorly understood. Genomic DNA was available from 98 patients with HCC, 77 familial controls, 97 controls from Hong Kong and 96 Northern European controls (NECs). Polymorphisms of interleukin (IL)-1beta; IL-1 receptor antagonist (IL-1RN); IL-10 promoter (positions -1082, -819, and -592); and tumor necrosis factor (TNF)-alpha promoter (TNF-a -238 and -308) were investigated. There was marked restriction in the distribution of the IL-1beta and IL-1RN genotypes among Chinese subjects with a predominance of the IL-1beta*1,1 and IL-1RN*1,1 (for unrelated controls compared with NECs only for IL-1beta: chi2 = 15.32, Pc = 0.000091 and for IL-1RN: chi2 = 16.08, Pc = 0.000061). For IL-10, the distribution of alleles was reversed in Chinese vs NECs. The TNFA*2 allele (TNFA -308 A), which is associated with high TNF-alpha production both in vivo and in vitro, was found in <10% of Chinese but was present in 33% of NECs (chi2 = 21.52, Pc <0.0000035). Though this study failed to highlight specific associations between any of the polymorphisms tested and the HCC in Hong Kong Chinese, the differences in the distribution of tested alleles may, in part, account for the increased susceptibility of the Chinese population to develop HCC.

Hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Chinese: a case-control study.

To assess whether hepatitis B and C virus infection were risk factors for hepatocellular carcinoma (HCC), antibody to hepatitis C virus (anti-HCV), hepatitis B surface antigen and e antigen (HBsAg and HBeAg) were tested in 150 HCC patients. Another 150 case-control pairs matched individually by sex and age were also enrolled. Univariate analysis demonstrated that both the anti-HCV and the carrier status of HBsAg and HBeAg were significantly associated with HCC. Multi-variate analysis revealed that both anti-HCV and HBsAg were risk factors for HCC. The population-attributable risk was estimated as 14.2% for anti-HCV alone, 59.4% for HBsAg alone and 8.0% for both anti-HCV and HBsAg in Taiwan. In conclusion, both hepatitis B and C virus infection are independent risk factors for HCC in Chinese in southern Taiwan.