Increased Risk Of HCC Research Articles

Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study

BackgroundHepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait.MethodsFifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient’s clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters’ estimates of the final model and used for interpretation of the model.ResultsThe HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9–193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2–173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2–43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04–0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05–0.71).ConclusionsThis study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.

Risk factors for HCC in contemporary cohorts of patients with cirrhosis.

Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk. We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% had cured HCV, 16.1% had alcoholic liver disease, and 30.1% had NAFLD. During 7406 person-years of follow-up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% CI,1.51-2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2-fold higher in patients with cured HCV (HR,2.04; 95% CI, 1.24-3.35). Current smoking (HR,1.63; 95% CI, 1.01-2.63) and overweight/obesity (HR,1.79; 95% CI, 1.08-2.95) were also associated with HCC risk. HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower risk in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.

Dietary N-Nitroso Compounds and Risk of Hepatocellular Carcinoma: A USA-Based Study.

N-nitroso compounds (NOCs) are among the most potent dietary carcinogens. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosopiperidine (NPIP) are abundant in foods and carcinogenic to the liver. We investigated the relationship between dietary NOCs and HCC risk. In this large, hospital-based, case-control study of 827 pathologically or radiologically confirmed HCC cases and 1,013 controls, NOC intake was calculated by linking food frequency questionnaire-derived dietary data with a comprehensive NOC concentration database. Multivariable-adjusted ORs and 95% CIs of HCC by quartiles of NOC consumption were estimated using logistic regression models, with the lowest quartile as the referent. We further investigated joint effects of consuming the highest quartile of NOCs that were associated with increased HCC risk and hepatitis, diabetes, or alcohol drinking on HCC risk. After adjustment for confounding factors, higher intake of NDEA from plant sources (ORQ4 vs. Q1 =1.58; 95% CI=1.03-2.41), NDMA from plant sources (ORQ4 vs. Q1 =1.54; 95% CI=1.01-2.34), and NPIP (ORQ4 vs. Q1 =2.52; 95% CI=1.62-3.94) was associated with increased HCC risk. No association was observed for nitrate or total NOC intake and HCC risk. Higher consumption of HCC-inducing NOCs and positive hepatitis virus status jointly increased the risk of developing HCC. In conclusion, though some of our findings may indicate the presence of reverse causation owing to lower meat intake among cases with chronic liver diseases before HCC diagnosis, the potent dietary HCC carcinogens, NDEA, NDMA, and NPIP, and their enhanced carcinogenic effects among chronic carriers of hepatitis virus warrant further prospective investigation.

Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis

Background & aimsHepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Effects of second-line oral antidiabetic medications on incident HCC risk in individuals with type 2 diabetes mellitus remain unclear. This study evaluated associations between sulfonylureas, thiazolidinediones, meglitinides and alpha-glucosidase inhibitors, and incident HCC risk. MethodsWe systematically reviewed all studies on PubMed, Embase and Web of Science databases. Studies were included if they documented: (1) exposure to oral antidiabetic medication classes; (2) HCC incidence; (3) relative risks/odds ratios (OR) for HCC incidence. Eight eligible observational studies were identified. We performed random-effects meta-analyses to calculate pooled adjusted ORs (aORs) and 95% confidence intervals (CI). ResultsThiazolidinedione use (7 studies, 280,567 participants, 19,242 HCC cases) was associated with reduced HCC risk (aOR = 0.92, 95% CI = 0.86–0.97, I2 = 43%), including among Asian subjects (aOR = 0.90, 95% CI = 0.83–0.97), but not Western subjects (aOR = 0.95, 95% CI = 0.87–1.04). Alpha-glucosidase inhibitor use (3 studies, 56,791 participants, 11,069 HCC cases) was associated with increased HCC incidence (aOR = 1.08; 95% CI = 1.02–1.14, I2 = 21%). Sulfonylurea use (8 studies, 281,180 participants, 19,466 HCC cases) was associated with increased HCC risk in studies including patients with established liver disease (aOR = 1.06, 95% CI = 1.02–1.11, I2 = 75%). Meglitinide use (4 studies, 58,237 participants, 11,310 HCC cases) was not associated with HCC incidence (aOR = 1.19; 95% CI = 0.89–1.60, I2 = 72%). ConclusionsThiazolidinedione use was associated with reduced HCC incidence in Asian individuals with diabetes. Alpha-glucosidase inhibitor or sulfonylurea use was associated with modestly increased HCC risk; future research should determine whether those agents should be avoided in patients with chronic liver disease.

Association between TNF-α, Interleukin-18 Polymorphisms and Risk of Hepatocellular Carcinoma in Egyptian patients.

Objective:To evaluate the association of gene polymorphisms of the SNP of TNF-α gene -238G>A and IL-18 gene-607C>A with the development of hepatocellular carcinoma among Egyptian patients. Methods:One hundred and fifty patients were allocated to this study; eighty patients with hepatocellular carcinoma (Group A), seventy cancer-free HCV age, and sex-matched patients (Group B). We analyzed two Single nucleotide polymorphisms (SNPs) (TNF-α-238G>A and IL-18-607C>A) by real-time polymerase chain reaction using sequence-specific primers (PCR-SSP). Results:Significant higher risk of HCC was associated with genotype IL-18–607AA (P<0.001), OR: 5(2.188-11.47), allele IL-18 -607⁄A (P=0.001), OR: 2.1(1.32-3.3). A significant association was found between the size of HFL in the HCC group and different genotypes of IL18 genes (P=0.013) where 62.5% of patients with tumor size >5 cm carried the risky (AA) genotype on the other hand the SNP of TNF-α gene -238G>A showed no statistically significant association between the two groups. Conclusion:The SNP -607C>A in the IL18 gene was associated with increased HCC risk in Egyptian patients suggesting its use as a potential diagnostic non-invasive tool that allows to identify a new group of HCC patients at an earlier stage.

One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment.

Background and aimsFibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy.MethodsA total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients.ResultsA total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48–9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B < 10 + 1-year FIB-4 < 1.30.ConclusionsIn non-cirrhotic CHB patients receiving prolonged NA therapy, 1-year FIB-4 < 1.30 is useful for identifying those with minimal HCC risk by combining with female sex or low PAGE-B score.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-020-10124-z.

Chitinase 3-like 1 gene (T/C) polymorphism and serum YKL-40 levels in patients with hepatocellular carcinoma

The chitinase 3-like 1 (CHI3L1) gene encodes the YKL-40 protein. Serum YKL-40 levels are controlled by polymorphisms in the CHI3L1 gene. We aimed to examine the association of the rs880633 (T/C) polymorphism in the CHI3L1 gene with serum YKL-40 levels and to evaluate the role of this polymorphism as a risk factor for HCC and its effect on patient survival. A total of 225 subjects were categorized into two groups: group I included 120 patients with HCC, and group II involved 105 age and gender-matched healthy volunteers. Genotypes of the rs880633 (T/C) polymorphism in the CHI3L1 gene were analyzed using an allele discrimination assay with real-time PCR, and serum YKL-40 levels were determined using an ELISA technique. A significant difference in the genotype frequency of the T/C polymorphism in the CHI3L1 gene was observed between the two groups, with an increase in the frequency of the CC genotype observed among patients with HCC. Regarding the allelic distribution, the C allele was significantly predominant in patients, with HCC presenting with an increased HCC risk compared to the T allele. Subjects with the CC genotype had the highest serum YKL-40 levels, followed by those with the TC genotype, while subjects with the TT genotype had the lowest serum YKL-40 levels. An analysis of the overall survival of HCC patients revealed that patients with both the CC and CT genotypes displayed a significantly shorter survival rate than patients carrying the TT genotype. ConclusionsThe rs880633 polymorphism in the CHI3L1 gene may be a risk element for HCC. Patients with the CC genotype displayed the highest serum YKL-40 levels, which were linked to poor prognosis.

161P - Chitinase 3-Like 1 gene (T/C) polymorphism and serum YKL-40 in hepatocellular carcinoma

BackgroundChitinase 3-like 1 (CHI3L1) gene codes for the YKL-40 protein. Serum YKL-40 levels are controlled by polymorphisms in the proximal promoter region of CHI3L1 gene. Aim: We aimed to investigate the association of rs880633 (T/C) polymorphism at CHI3L1 gene with serum YKL-40 production and to evaluate the role of this polymorphism as a risk for HCC and its impact on patient’s survival. Methods225 subjects were classified into two groups, group I: included 120 HCC patients and group II: included 105 age & gender matched healthy volunteers. Genotyping of (T/C) polymorphism rs880633 at CHI3L1 gene was analyzed using allelic discrimination assay by Real-Time PCR technique and serum YKL-40 level was determined by ELISA. ResultsThere was a significant statistical difference as regards genotype frequency of CHI3L1 gene T/C polymorphism between the two studied groups, with increased frequency of CC genotype among HCC patients and increased frequency of TT genotype among the control group. As regards allelic distribution, C allele was significantly more dominant in HCC patients that have increased HCC risk with odds ratio (CI = 95%) of 2.05(1.40 – 2.99) comparing to T allele. Subjects carrying CC genotype had the highest levels serum YKL40 followed by those with TC genotype, while subjects with TT genotype were found to have the lowest serum YKL40. HCC Patient with TT genotype had significantly longer survival rate than those had TC, CC genotypes, Overall survival of HCC patients revealed that both CC and CT genotypes had significantly shorter survival rate than those had TT genotype (P value <0.05). ConclusionsCHI3L1 gene variants rs880633 might be a candidate risk factor for HCC. Carriers of CC genotype have highest serum YKL40 levels, are associated with criteria of bad prognosis. So, genotyping of (T/C) polymorphism rs880633 at CHI3L1 gene could predict the patient outcome. Legal entity responsible for the studyMenoufia University. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Abstract LB-150: Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection

Abstract Background: Direct acting antiviral medications (DAA) have become the mainstay for treatment of chronic hepatitis C virus (HCV) infection. However, some studies have suggested an increased risk of HCC development following use of DAAs for HCV compared with use of interferon-based medications (IFN), while other studies, mostly in Veterans Administration population in the United States, did not show an increase in HCC risk after the use of DAA in patients with HCV. To address these conflicting reports, we investigated the association between use of DAA for HCV and subsequent development of HCC in a large, longitudinal data with broad representation of individuals from various ages, ethnicities, and geographic regions across the United States. Methods: A retrospective cohort study was performed using medical and pharmacy claims from the OptumLabs® Data Warehouse. The study included 9,532 incident HCV cases (2010-2016) of ages 18 years or older treated with DAA or IFN and did not have a prior diagnosis of HCC before initiation of the antiviral therapy. The participants were categorized into DAA-only or IFN-only groups. To account for confounding by indication, inverse probability of treatment weighting (IPTW) was performed to ensure balance in sociodemographic and treatment related factors between treatment groups. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC risk, comparing DAA-only regimen with IFN-only regimen (reference). Results: Median follow-up for the entire study cohort was 1.4 years, with a slightly longer follow-up for individuals in the IFN-only group (1.8 years) than for those in the DAA-only group (1.4 years). One hundred and seventy-one incident HCC cases developed during follow-up, with a higher occurrence of HCC in the DAA-only group (n=155; 11.9 cases per 1,000 person-years) than in the IFN-only group (n=16; 8.3 cases per 1,000 person-years). Compared with IFN-only treatment, use of DAA-only for HCV was not associated with an increase in HCC risk (HR=1.47, 95% CI: 0.89-2.42). Similarly, no association was found between use of DAA-only regimen and HCC risk among individuals with cirrhosis (HR=1.28, 95% CI: 0.71-2.31) or those without cirrhosis (HR =1.80, 95% CI: 0.64-5.03). When stratified by sustained virologic response (SVR), a measure of complete viral clearance, we noted a higher HCC risk associated with DAA-only regimen among individuals with SVR (HR=7.83, 95% CI: 1.54-39.88) and a lower risk for DAA-only regimen among those without SVR (HR=0.12, 95% CI: 0.02-0.95); however, the CIs are substantially wide, reflecting the small numbers in these subgroup analyses. Conclusion: Despite some prior reports of increased risk of HCC development following use of DAA for HCV, this ethnically and geographically diverse study did not find compelling evidence indicating an increased HCC risk associated with use of DAA in patients with HCV when compared with use of IFN. Citation Format: Samuel O. Antwi, Holly K. Van Houten, Lindsey R. Sangaralingham, Tushar Patel. Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-150.

Increased HCC risk in cirrhosis patients treated with DAAs?

Increased HCC risk in cirrhosis patients treated with DAAs?

The association of lncRNA-HULC polymorphisms with hepatocellular cancer risk and prognosis

BackgroundGenetic polymorphisms in lncRNA HULC may affect the susceptibility and clinical outcome of cancer. We aimed to investigate the association of HULC tagSNPs with the risk and prognosis of hepatocellular cancer, as well as the influence of the SNPs on lncRNA expression level. MethodsA total of 1338 samples were recruited in the risk study. Among them, 351 HCC patients were involved in the prognosis study. SNP genotyping was performed using KASP method and lncRNA expression was detected by Real-time PCR. ResultsWe found a promoter SNP, rs1041279, was associated with a 1.41-fold increased HCC risk (P = 0.032). In the stratified analysis, rs1041279 had greater ORs for the increased HCC risk in the male subgroup (P = 0.014, OR = 1.54). Furthermore, multi-logistic regression analysis revealed a two-way interaction effect of smoking-rs2038540 SNP on HCC risk (OR = 4.20). And MDR analysis consistently demonstrated a SNP–environmental interaction among smoking-drinking-rs2038540 SNP as the best model for predicting HCC risk (P = 0.0107). In our study, no significant association was found between HULC SNPs and the overall survival (P > 0.05), and no significant effect was observed of rs1041279 SNP on lncRNA-HULC expression (P > 0.05). ConclusionlncRNA-HULC rs1041279 SNP and the interaction of rs2038540 SNP with environmental factors could enhance HCC risk.

Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection

Hepatocellular (HCC) surveillance guidelines for patients with chronic hepatitis B virus (HBV) infection are based on race- and age-specific estimates of HCC risk, derived from studies conducted in areas in which HBV is endemic. We conducted a retrospective cohort study using the national Veterans Administration data to identify patients with chronic HBV infection from 2001 through 2013. We examined the effect of race and age on HCC risk while adjusting for baseline clinical characteristics. The study cohort had 8329 patients; 3498 patients (42.0%) were white, 3248 (39%) were African Americans, and 659 (7.9%) were Asian Pacific Islanders. The annual HCC incidence was highest in Asian Pacific Islanders (0.65%), followed by whites (0.57%) and African Americans (0.40%). After adjusting for clinical and viral factors, the risk of HCC was significantly higher inAsian Pacific Islanders compared with whites (adjusted hazard ratio [HR]= 2.04; 95% CI, 1.31-3.17). There was no difference in HCC risk between African Americans and whites (adjusted HR, 0.77; 95% CI, 0.58-1.02). HCC risk increased with age: adjusted HR was 1.97 (95% CI, 0.99-3.87) for 40-49 years; adjusted HR was 3.00 (95% CI, 1.55-5.81) for 50-59 years; and adjusted HR was 4.02 (95% CI, 2.03-7.94) for more than 60 years vs less than 40 years. Patients with cirrhosis had higher risk of HCC than patients without cirrhosis (adjusted HR= 3.69; 95% CI, 2.82-4.83). However, even among patients without cirrhosis, the annual incidence of HCC was more than 0.2% for all patients older than 40 years with high levels of alanine aminotransferase-regardless of race. In a sample of male veterans with chronic HBV infection, risk of HCC is highest among Asian Pacific Islanders, followed by whites and African Americans. Cirrhosis increased HCC risk. Among patients without cirrhosis, male patients who are older than 40 years and have increased levels of alanine aminotransferase might benefit from HCC surveillance, regardless ofrace.

Telomere Length and Risk of Hepatocellular Carcinoma: A Nested Case–Control Study in Taiwan Cancer Screening Program Cohort

Telomere length (TL) measured in peripheral blood leucocytes (PBL) might be a useful biomarker to identify elevated cancer risk. A case-control study which included 268 newly-diagnosed HCC cases and 536 matched controls, was conducted. Absolute TL in PBL was analyzed by quantitative real-time PCR. The overall median length of TL was not statistically shorter in HCC cases compared to healthy controls. However, we found a significant synergistic effect of longer TL and HCV infection to increase HCC risk with a relative excess risk of 6.86 (95% CI: 2.14-11.58). Among HCC cases, significant shorter TLs were observed for <5 years (OR=3.93, 95% CI: 2.00-7.72); 5-10 years (OR=2.16, 95% CI: 1.10-4.24) compared to >10 years prior to diagnosis. Shorter PBL TL alone was not significantly associated with increased HCC risk. Among HCC cases, significant shorter TLs were observed for <5 years prior to diagnosis.

Three polymorphisms of tumor necrosis factor-alpha and hepatitis B virus related hepatocellular carcinoma: A meta-analysis.

To assess the association between tumor necrosis factor-alpha (TNF-α) G308A, G238A and C863T polymorphisms and hepatitis B virus related hepatocellular carcinoma (HBV-HCC) susceptibility. We interrogated the databases of Pubmed, Sciencedirect and Viley online library up to March 8, 2016. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated in a fixed-effects model or a random-effects model when appropriate. In total, 12 case-control studies which containing 1580 HBV-HCC cases, 2033 HBV carrier controls, 395 HBV spontaneously recovered (SR) controls and 1116 healthy controls were included. Compared with GG genotype, the genotypes GA/AA of G308A were associated with a significantly increased HBV-HCC risk when the controls were all healthy individuals (AA vs. GG, OR 2.483, 95%CI 1.243 to 4.959; GA vs. GG, OR 1.383, 95%CI 1.028 to 1.860; GA/AA vs. GG, OR 1.381, 95%CI 1.048 to 1.820). Meanwhile, only the AA vs. GG model of G238A and HBV-HCC showed a statistic significance when the controls were healthy individuals (OR 4.776, 95%CI 1.280 to 17.819). CT genotype of TNF-α C863T could increase HBV-HCC risk whenever the controls were healthy individuals, HBV carriers or HBV recovers. This meta-analysis shows that AA genotype in TNF-α G308A and TNF-α G238A and CT genotype in TNF-α C863T may increase HBV-HCC risk. Therefore, HBV infection seemed to be a more important factor for tumorigenesis of HCC than genetic predisposition in G308A of TNF-α, and interaction between TNF-α C863T polymorphisms and HBV infection might be associated with increased HCC risk.

An let-7 KRAS rs712 polymorphism increases hepatocellular carcinoma risk.

KRAS, also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, acts as an intracellular signal transducer. The oncogenic KRAS mutation is an essential step in the development of many types of human cancers, including hepatocellular carcinoma. Here we aimed to investigate the relationship between KRAS rs712 polymorphisms and hepatocellular carcinoma susceptibility. Five-hundred-and-fourteen participants were enrolled in a case-control study (262 cases and 252 normal subjects). The variants were distinguished using polymerase chain reaction-restriction fragment length polymorphism. Significantly increased HCC risk was observed to be associated with the T allele of the rs712 locus (P = 0.049, OR = 1.35, 95%CI = 1.01-1.78). Further, HCC risk with the GT genotype (P = 0.015, OR = 1.64, 95%CI = 1.08-2.50) and the TT genotype (P = 0.015, OR = 2.56, 95%CI = 1.05-6.25) in a codominant model was significantly higher than that with the GG genotype. In a dominant model, significantly increased HCC susceptibility was also associated with T allele carriers (P = 0.006, OR = 1.75, 95%CI = 1.16-2.63). Moreover, we found that the frequency of the KRAS rs712 TT genotype was significantly higher in HBV-positive HCC patients than in HBV-negative HCC patients.

Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population

Background and objectiveInterleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual’s susceptibility to hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with HBV-related HCC in a Chinese population. MethodsThe +114T/G and −384T/G polymorphisms in the IL-2 gene were examined in 115 cases of chronic hepatitis B (CHB), 67 cases of HBV-related liver cirrhosis (LC), 107 cases of HBV-related HCC, and 105 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). ResultsWe found that there were significant differences in the genotype and allele frequencies of the IL-2 gene +114T/G polymorphism between the HBV-related HCC patients and the healthy controls. The +114 TG and GG genotypes were associated with a significant increased HCC risk as compared with the TT genotype (OR=1.988, 95% CI, 1.034–3.480, P=0.009 for TG genotype, and OR=1.975, 95% CI, 1.012–3.341, P=0.013 for GG genotype, respectively). The +114 G allele was correlated with a significant increased HCC risk as compared with the T allele (OR=1.423, 95% CI, 1.023–1.975, P=0.031). In addition, we found significant decreased serum IL-2 in HBV-related HCC patients (288.6±177.1ng/L) compared with healthy controls (238.2±136.7ng/L) (t=2.32, P=0.021). Genotypes carrying the +114 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in HBV-related HCC patients. ConclusionThe results suggested that the IL-2 +114T/G polymorphism may contribute to increased HBV-related HCC risk through regulating the serum IL-2 levels. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.