Hepatocellular Carcinoma In Chinese Population Research Articles

A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population.

This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS). A case-control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta-analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models. A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84-0.89; AUC: 0.85, 95% CI: 0.81-0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60-0.67; AUC: 0.65, 95% CI: 0.60-0.71). A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at-risk individuals for precise prevention.

Risks and Clinical Predictors of Hepatocellular Carcinoma in Chinese Populations: A Real-World Study of 10,359 Patients in Six Medical Centers.

Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China. A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up. Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis. The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.

Using the aMAP Risk Score to Predict Late Recurrence Following Radiofrequency Ablation for Hepatocellular Carcinoma in Chinese Population: A Multicenter Study.

ObjectiveThis study was conducted to explore the application of age-male-ALBI-platelets (aMAP) score for predicting late recurrence of hepatocellular carcinoma (HCC) following radiofrequency ablation (RFA) and develop an aMAP score based-nomogram to predict prognosis in Chinese population.Materials and MethodsHCC patients who developed late recurrence following RFA at National Cancer Center (NCC) of China, First Hospital of Shanxi Medical University and Beijing Hospital of Traditional Chinese Medicine from January 2011 to December 2016 were included as a training cohort, and patients who were treated at Affiliated Cancer Hospital of Zhengzhou University between January 2012 and December 2016 were included as an external validation cohort. The optimal cut-off value for aMAP score was determined using X-tile software to discriminate the performance of recurrence-free survival (RFS).ResultsA total of 339 eligible patients were included in this study. Patients were grouped into low-risk (aMAP score ≤64.2), medium-risk (64.3 ≤aMAP score ≤68.6) and high-risk (aMAP score ≥68.7) groups by X-tile plots. The prognostic factors that affected RFS were the number of lesions and aMAP score. A nomogram was constructed to predict the RFS with a C-index of 0.793 (95% CI: 0.744–0.842). The time-dependent receiver operating characteristic curves (t-AUCs) of the nomogram to predict 3, 4 and 5-year RFS were 0.808, 0.820 and 0.764, respectively. The model was then tested with data from an external validation cohort. The calibration curve confirmed the optimal agreement between the predicted and observed values.ConclusionThe aMAP score provided a well-discriminated risk stratification and is an independent prognostic factor for the late recurrence of HCC following RFA. The aMAP score-based nomogram could help to strengthen prognosis-based decision making and formulate adjuvant therapeutic and preventive strategies.

Contribution of Hepatitis B Virus Infection to the Aggressiveness of Primary Liver Cancer: A Clinical Epidemiological Study in Eastern China

Background and aims: The contribution of hepatitis B virus (HBV) infection to the aggressiveness of primary liver cancer (PLC) remains controversial. We aimed to characterize this in eastern China.Methods: We enrolled 8,515 PLC patients whose specimens were reserved at the BioBank of the hepatobiliary hospital (Shanghai, China) during 2007–2016. Of those, 3,124 who received primary radical resection were involved in survival analysis. A nomogram was constructed to predict the survivals using preoperative parameters.Results: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular cholangiocarcinoma (CHC) accounted for 94.6, 3.7, and 1.7%, respectively. The rates of HBV infection were 87.5, 49.2, and 80.6%, respectively. HBV infection was significantly associated with 10-year earlier onset, more cirrhosis, higher α-fetoprotein, higher carbohydrate antigen 19-9 (CA19-9), more microvascular invasion (MVI), lower neutrophil-to-lymphocyte ratio (NLR), and lower platelet-to-lymphocyte ratio (PLR) in HCC. HBV infection was also associated with 7-year earlier onset, more cirrhosis, higher α-fetoprotein, more MVI, and lower PLR in ICC. In the multivariate Cox analysis, high circulating HBV DNA, α-fetoprotein, CA19-9, NLR, tumor size, number, encapsulation, Barcelona Clinic Liver Cancer (BCLC) stage, and MVI predicted an unfavorable prognosis in HCC; only CA19-9 and BCLC stage, rather than HBV-related parameters, had prognostic values in ICC. A nomogram constructed with preoperative HBV-related parameters including HBV load, ultrasonic cirrhosis, and α-fetoprotein perform better than the current staging systems in predicting postoperative survival in HCC.Conclusion: HBV promotes the aggressiveness of HCC in Chinese population. The contributions of HBV to ICC and other etiological factors to HCC might be indirect via arousing non-resolving inflammation.

Breast cancer risk-associated variants at 6q25.1 influence risk of hepatocellular carcinoma in a Chinese population.

The gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of estrogens in HCC pathogenesis. In this study, we conducted a case-control study to investigate whether breast cancer risk-associated single nucleotide polymorphisms (SNPs) located at estrogens loci identified by genome-wide association studies (GWASs) also predispose to HCC in a Chinese population. Three candidate SNPs at 6q25.1 were genotyped in 2025 HCC cases and 2032 healthy controls. Differential expression analyses and expression quantitative trait loci (eQTL) analyses were conducted to further explore the potential function of significant SNPs and genes they reside in. Two of the three candidate SNPs (rs9383951 and rs9485372) were observed to be significantly associated with HCC risk. Under a dominant model, the odds ratios (OR) for rs9383951 and rs9485372 were 1.28 (95% CI: 1.10-1.49, P = 0.002) and 1.34 (95% CI: 1.17-1.53, P = 2.75 × 10-5), respectively. We also found a significant accumulative effect of these two SNPs and there was a gradual increase in OR with a greater number of hazard genotypes. Moreover, the association between rs9383951 and HCC risk was specific in males. Lower ESR1 and TAB2 expressions were investigated in hepatic tumor tissues than adjacent normal tissues. We found a significant association between rs9383951 and ESR1 expression (P = 0.047). Besides, ESR1 expression was significantly correlated with the expression of TAB2. Taken together, our study identified two genetic variants at 6q25.1 newly associated with HCC risk, suggesting ESR1 and estrogen signaling may play a role in mediating susceptibility to HCC in Chinese population.

Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis

The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls. Seventeen differential MAL-associated glycoproteins were identified. Among them, Galectin 3 binding protein (Gal-3BP) was selected for further evaluated by ELISA analysis and showed a high diagnostic potential of HBV-related HCC, with the AUC of 0.898 and a sensitivity, specificity and accuracy of 80.00%, 93.75% and 86.88%, respectively. Moreover, we constructed a predictive model through the combined use of serum Gal-3BP and Alpha Fetoprotein (AFP), which improved the sensitivity (from 87.5% to 95%), specificity (from 93.75% to 95%) and accuracy (from 90.63% to 95%) of diagnosing early HCC. These data suggested serum Gal-3BP level is a promising biomarker to identify HBV-related HCC and the combined use of serum Gal-3BP and AFP improves the diagnostic potential of HBV-HCC compared with AFP alone in current clinical practice.

Association of polymorphisms in the heparanase gene (HPSE) with hepatocellular carcinoma in Chinese populations.

Heparanase activity is involved in cancer growth and development in humans and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be associated with tumors. In this study, we investigated whether SNPs in HPSE were a risk factor for hepatocellular carcinoma (HCC) by undertaking a comprehensive haplotype-tagging, case-control study. For this, six haplotype-tagging SNPs (htSNPs) in HPSE were genotyped in 400 HCC patients and 480 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A log-additive model revealed significant correlations between the HPSE polymorphisms rs12331678 and rs12503843 and the risk of HCC in the overall samples (p = 0.0046 and p = 0.0055). When the analysis was stratified based on hepatitis B virus (HBV) carrier status, significant interactions between rs12331678 and rs12503843 and HBV were observed. Conditional logistic regression analysis for the independent effect of one significant SNP suggested that rs12331678 or rs12503843 contributed an independent effect to the significant association with the risk of HCC, respectively. Our findings suggest that the SNPs rs12331678 and rs12503843 are HCC risk factors, although the potential functional roles of these two SNPs remain to be fully elucidated.

Abstract 1226: Association of p53 codon72 polymorphism with susceptibility to hepatocellular carcinoma in Chinese population of Northeast Sichuan

Abstract Hepatocellular carcinoma (HCC) is commonly known as”the king of cancer”, with high mortality and low survival due to advanced stage and poor clinical outcomes worldwide. Development of HCC is a multistep process which involves in genetic factors such as alterations of oncogenes and tumor suppressor genes, and environmental exposure like viral infections and aflatoxin contamination as well. The p53 tumor suppressor protein plays key roles in tumor development and progression, and single nucleotide polymorphism (SNP) of the p53 gene codon 72 (P53Arg/Pro) changes the structure of the protein and affects its activity which might affect cancer risk. Data showed that the prevalence of P53Arg/Pro different genotypes varied with race and geographic location, and previous studies provided controversial findings about the association of P53Arg/Pro and HCC incidences. A case-control study here was employed to investigate the associations between p53 codon72 polymorphism and HCC susceptibility in Chinese population of northeast Sichuan. A total of 150 subjects with HCC and 341 cancer-free control subjects were involved in this study. Genomic DNA was extracted from peripheral blood and the p53 codon72 polymorphism was measured by Taqman MGB, a fluorescent quantitative real time PCR assay. The distribution frequency of p53 sites was compared between the HCC group and the control, including the stratified and interaction analysis of the related environmental factors about HCC in order to understand the roles of p53 codon72 polymorphism and environmental factors in the development of HCC. The results showed that the distribution frequency of p53 sites of Arg/Arg, Arg/Pro, Pro/Pro were 18.0%, 48.7%, 33.3% in HCC group,and 16.4%, 47.8%, 35.8% in the control respectively, which indicated that there was no obvious differences between the two groups. Further stratified with smoking, alcohol drinking, gender, HBV infection,no risk increasing genotype was found either. However, interactions between p53 codon72 polymorphism and above environmental conditions exposure might increase the risk of HCC(smoking OR = 2.18,95%CI:1.12-4.25), (gender OR = 3.01,95%CI:1.00-9.14), (HBV infection OR = 6.05,95%CI:2.29-16.00), respectively. Our findings indicated that no significant association was found between p53 codon72 polymorphism and the susceptibility to HCC in Chinese population of Northeast Sichuan currently.; However, interaction between genetic factors and environment exposure significantly increased the risk of HCC. This study suggests some environmental exposure control measures, such as smoking cessation, hepatitis B vaccination and early screening for men at high-risk age, which could be taken to effectively prevent the development of HCC. Citation Format: Jiajing Cai, Yan Cai, Qiang Ma, Dongsheng Wang, Guoyuan Zhang, Xiaolan Guo. Association of p53 codon72 polymorphism with susceptibility to hepatocellular carcinoma in Chinese population of Northeast Sichuan. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1226. doi:10.1158/1538-7445.AM2015-1226

Genetic polymorphisms in antioxidant enzyme genes and susceptibility to hepatocellular carcinoma in Chinese population: a case-control study.

An increased oxidant burden has been implicated in hepatocarcinogenesis, and several antioxidant enzymes counteract potential oxidative damage. So, polymorphisms in the genes encoding antioxidant enzymes may play an important role in the development of hepatocellular carcinoma (HCC). To test this hypothesis, we investigated the association of polymorphisms in antioxidant enzyme genes, including three superoxide dismutases (SODs), catalase (CAT), and glutathione peroxidase (GPx), with HCC in a Chinese population consisting of 434 HCC patients and 480 control subjects. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were estimated by unconditional logistic regression. For the ECSOD Ala40Thr polymorphism, a significant association was observed between this polymorphism and HCC risk in non-hepatitis B virus (HBV) carriers but not in HBV carriers, and individuals with one 40Thr allele (Ala/Thr genotype) (OR = 2.13, 95 % CI = 1.25-3.64, P = 0.006) or at least one 40Thr allele (Ala/Thr and Thr/Thr genotype) (OR = 1.90, 95 % CI = 1.15-3.15, P = 0.012) showed significantly higher risk to HCC, compared with Ala/Ala genotype. No significant associations were observed between three other polymorphisms (MnSOD Ala16Val, CAT-262C/T, GPx Pro198Leu) and HCC susceptibility in both HBV carriers and non-HBV carriers. Furthermore, no other signs of combined effects, except for a combined effect of ECSOD Ala40Thr and MnSOD Val16Ala in non-HBV carriers, were observed for each combination of these four polymorphisms. In conclusion, our results indicate that the antioxidant enzyme gene polymorphisms at least partially contribute to the susceptibility to HCC.

Polymorphisms of the CYP1B1 gene and hepatocellular carcinoma risk in a Chinese population

BackgroundCYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as estrogen metabolism. We hypothesized that genetic variants in CYP1B1 may modify individual susceptibility to hepatocellular carcinoma (HCC). MethodsTo test this hypothesis, we evaluated the associations of three CYP1B1 single nucleotide polymorphisms (SNPs) and HCC risk in a case–control study of 468 HCC cases and 515 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were performed to detect these polymorphisms. ResultsIn overall analysis, we found that only the variant G allele of rs1056836 was associated with a significantly increased risk of HCC among the three SNPs (rs10012, rs1056836 and rs1800440). Moreover, we found that the variant genotypes containing the G allele of rs1056836 were associated with a significantly increased risk of HCC among HbsAg-positive individuals (adjusted OR=2.13, 95% CI=1.18, 3.86), but not among HbsAg-negative individuals. When stratifying by smoking status, we found that the variant GG genotype increased a 13.97-fold (95% CI=1.28, 152.94) risk of HCC among smokers. Furthermore, high risk for liver cirrhosis-positive clinical status was exhibited in HCC patients with rs1056836 CG and GG genotypes as compared with CC homozygotes. For the other two SNPs, we did not find any significant evidence of association with HCC risk in any subgroup. ConclusionThis study suggests that CYP1B1 rs1056836 polymorphism may be an important factor contributing to increased susceptibility and pathological development of HCC in Chinese population.

Evaluation of eight different clinical staging systems associated with overall survival of chinese patients with hepatocellular carcinoma.

Background:Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients.Methods:This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic.Results:The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7th (TNM 7th) (AIC = 2899.980), TNM 6th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389).Conclusions:BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Association between XRCC1 Arg399Gln polymorphism and susceptibility to hepatocellular carcinoma in Chinese populations: A Meta-analysis

Association between XRCC1 Arg399Gln polymorphism and susceptibility to hepatocellular carcinoma in Chinese populations: A Meta-analysis

PO-0981 A Novel Mutation Of Ipex Syndrome In A Paediatric Patient

Background Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder characterised by multiple autoimmunity. Mutations in the fork head box P3 (FOXP3) gene, in chromosome Xp11.23, result in reduced numbers or a complete absence of CD4 + regulatory T (Treg) cells and therefore in a variety of clinical presentation. Methods We present the case of a 3-year old male with clinical and laboratory findings of IPEX and a novel mutation of the FOXP3 gene. Results A 3-year Chinese male was admitted to the 3rd Clinic of the First Paediatrics of University of Athens, Greece, due to critical malnutrition. Severe diarrhoea and malabsorption were the predominant symptoms; therefore the administration of long term TPN was essential. The patient underwent a colonoscopy which revealed autoimmune enteropathy, while Diabetes type I, the other major clinical finding, required strict dietary program and insulin administration. Our patient was set on steroids and azathioprine, which was withdrawn however due to cholestasis on day 107. Patient’s laboratory findings were constant with immunodeficiency (low immunoglobulins IgA and IgM), nevertheless, the flow cytometry revealed normal number of CD4 + /CD25 + regulatory cells. Under the strong suspicion of IPEX syndrome, a molecular analysis was performed and a novel mutation, c.1161G-p. H387Q in FOXP3 gene was identified, confirming the diagnosis. Conclusions A total of 13 allelic variants in FOXP3 have been described so far, leading into different phenotypes of IPEX syndrome. The genetic variant c.1161G has been associated with hepatocellular carcinoma in Chinese population, but has never been reported in IPEX syndrome.

Functional short tandem repeat polymorphism of PTPN11 and susceptibility to hepatocellular carcinoma in Chinese populations.

Background PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations.Methodology/Principal FindingsWe analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.53–0.76, P = 2.00×10−7], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34–0.62, P = 1.00×10−7). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA.Conclusions/SignificanceTaken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.

Genetic polymorphisms of XRCC1 gene and susceptibility to hepatocellular carcinoma in Chinese population

Hepatocellular carcinoma (HCC) is a common cancer in the worldwide. Accumulated evidences indicate that genetic polymorphisms of human X-ray repair complementing group 1 gene (XRCC1) are associated with the susceptibility to HCC. This study aims to investigate the potential association between XRCC1 c.482C>T and c.1178G>A genetic polymorphisms and the susceptibility to HCC. A total of 1,069 Chinese Han subjects consisting of 530 HCC patients and 539 cancer-free controls were recruited in this case-control study. The created restriction site-polymerase chain reaction and directly DNA sequencing methods were utilized to analyze the genotyping of XRCC1 genetic polymorphisms. Our data suggested that the XRCC1 c.482C>T and c.1178G>A genetic polymorphisms were statistically associated with the increased risks of HCC [for c.482C>T, TT vs. CC: OR 2.05, 95% CI 1.26-3.32, P = 0.003; T vs. C: OR 1.26, 95% CI 1.04-1.51, P = 0.017; for c.1178G>A, AA vs. GG: OR 2.15, 95% CI 1.26-3.67, P = 0.004; A vs. G: OR 1.33, 95% CI 1.10-1.61, P = 0.004]. The allele-T and genotype-TT of c.482C>T and allele-A and genotype-AA of c.1178G>A genetic polymorphisms may enhance the susceptibility to HCC. Our findings indicate that the studied XRCC1 genetic polymorphisms may influence the risk of HCC in Chinese populations and might be used as molecular markers for assessing the risk of HCC.

Association analysis between the c.1804C>A genetic polymorphism of XRCC1 gene and risk of hepatocellular carcinoma in Chinese population

Hepatocellular carcinoma (HCC) is a common liver malignancy in the world. The X-ray repair cross-complementing group 1 gene (XRCC1) is one of the most important candidate genes for influencing HCC risk. The purpose of this study was to evaluate the association between genetic polymorphisms of XRCC1 and HCC risk. A total of 592 HCC patients and 594 healthy controls were recruited in this case-control study. The c.1804C>A genetic polymorphism of XRCC1 gene was genotyped by the created restriction site-polymerase chain reaction and DNA sequencing methods. Our data suggested that the c.1804C>A genetic polymorphism of XRCC1 gene was significantly associated with the increased risk of HCC in the homozygote comparison (AA vs. CC: odds ratio (OR) 1.92, 95% confidence interval (CI) 1.25-2.94, P=0.003), recessive model (AA vs. OR 1.93, 95% CI 1.28-2.92, P=0.002), and allele comparison (A vs. C: OR 1.20, 95% CI 1.00-1.42, P=0.045). The allele A and genotype AA might contribute to the susceptibility to HCC. Our findings support that c.1804C>A genetic polymorphism of XRCC1 gene plays a genetic influence on the susceptibility to HCC in the studied population.

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case-control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR) = 1.09, 95 % confidence interval (95% CI) 1.01-1.17; TT versus CC, OR = 1.17, 95% CI 1.00-1.38; TT/CT versus CC, OR = 1.12, 95% CI 1.00-1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR = 0.65, 95% CI 0.46-0.91; CC versus AA/AC, OR = 0.64, 95% CI 0.46-0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.

Association between the c.1564A>T genetic polymorphism of the MDR1 gene and hepatocellular carcinoma in Chinese population.

OR = 1.64, 95%CI = 1.15-2.33, χ(2) = 7.66, P = 0.006), and allele contrast (T versus A: OR = 1.23, 95%CI = 1.04-1.45, χ(2) = 6.09, P = 0.014). Our data suggest that the genotypes/alleles from c.1564A>T genetic polymorphisms are statistically associated with HCC risk. The allele-T and genotype TT may contribute to susceptibility to HCC in the Chinese Han population.

Association analysis between MDR1 gene polymorphisms and risk of hepatocellular carcinoma in Chinese population

The objective of this study was to evaluate the association between MDR1 gene polymorphisms and hepatocellular carcinoma (HCC) risk. Genomic DNA of 1431 subjects was extracted from peripheral blood and genotyping was performed using the created restriction site-polymerase chain reaction (CRS-PCR). We found that the c.1465C > T single nucleotide polymorphisms (SNP) increased HCC risk in all genetic models (p < 0.05) and the allele-T of c.1465C > T may contribute to the risk of HCC. No significantly increased HCC risk was detected in c.159G > T SNP. Our data indicated that the genetic variants of MDR1 gene may be a valuable molecular marker for HCC.

Insertion/Deletion Polymorphisms in the Promoter Region of BRM Contribute to Risk of Hepatocellular Carcinoma in Chinese Populations

BackgroundBRM (Brahma homologue) is well known for its critical role in tumor suppression and cancer development. Genetic variations in the promoter region of BRM have been suggested to be associated with loss of BRM expression and lung cancer risk. To the authors’ knowledge, no study on the role of BRM genetic polymorphisms in hepatocellular carcinoma (HCC) risk has been performed.Methodology/Principal FindingsIn two independent case-control studies containing 796 HCC cases and 806 cancer-free individuals, we genotyped two putative functional insertion/deletion (indel) polymorphisms [BRM-1321 (rs3832613) and BRM-741 (rs34480940)] within promoter region of BRM in Chinese populations using a PCR-based method. Real-time RT-PCR analysis was used to explore the genotype-phenotype correlation between these polymorphisms and BRM expression in both tissue samples and HCC cell lines. Logistic regression analysis showed that compared to BRM-1321del/del genotype, the ins/del and ins/ins variant genotypes had an increased HCC risk [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.19–1.82; adjusted OR = 2.55, 95% CI = 1.75–3.72, respectively]. No significant association between BRM-741 and HCC incidence was observed. However, stratification analysis revealed a significant association between ins/ins genotype of BRM-741 and increased HCC susceptibility in smokers (adjusted OR = 2.07, 95% CI = 1.33–3.22). Quantitative PCR analyses demonstrated that the genotypes of BRM-1321 and the corresponding haplotypes were significantly correlated with BRM expression in vivo. Compared with ins/ins genotype, subjects carrying ins/del and del/del genotype had 2.30 and 4.99 fold higher BRM expression in HCC tissue samples, respectively. Similar trends were observed in western blot analysis at protein level.Conclusions/SignificanceOur findings suggest that BRM promoter polymorphism (BRM-1321) could regulate BRM expression and may serve as a potential marker for genetic susceptibility to HCC.