Toxicogenomics scoring system: TGSS, a novel integrated risk assessment model for chemical carcinogenicity prediction.

BACKGROUND: Given the increasing exposure of humans to environmental chemicals and the limitations of conventional toxicity test, there is an urgent need to develop next-generation risk assessment methods. OBJECTIVES: This study aims to establish a novel computational system named Toxicogenomics Scoring System (TGSS) to predict the carcinogenicity of chemicals coupling chemical-gene interactions with multiple cancer transcriptomic datasets. METHODS: Chemical-related gene signatures were derived from chemical-gene interaction data from the Comparative Toxicogenomics Database (CTD). For each cancer type in TCGA, genes were ranked by their effects on tumorigenesis, which is based on the differential expression between tumor and normal samples. Next, we developed carcinogenicity scores (C-scores) using pre-ranked GSEA to quantify the correlation between chemical-related gene signatures and ranked gene lists. Then we established TGSS by systematically evaluating the C-scores in multiple chemical-tumor pairs. Furthermore, we examined the performance of our approach by ROC curves or prognostic analyses in TCGA and multiple independent cancer cohorts. RESULTS: Forty-six environmental chemicals were finally included in the study. C-score was calculated for each chemical-tumor pair. The C-scores of IARC Group 3 chemicals were significantly lower than those of chemicals in Group 1 (P-value = 0.02) and Group 2 (P-values = 7.49 ×10-5). ROC curves analysis indicated that C-score could distinguish "high-risk chemicals" from the other compounds (AUC = 0.67) with a specificity and sensitivity of 0.86 and 0.57. The results of survival analysis were also in line with the assessed carcinogenicity in TGSS for the chemicals in Group 1. Finally, consistent results were further validated in independent cancer cohorts. CONCLUSION: TGSS highlighted the great potential of integrating chemical-gene interactions with gene-cancer relationships to predict the carcinogenic risk of chemicals, which would be valuable for systems toxicology.

lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150.

Long noncoding RNAs (lncRNAs) CASC11 is an oncogenic lncRNA in gastric cancer and colorectal cancer. Our study aimed to investigate the role of lncRNA CASC11 in bladder cancer. In this study we showed that plasma lncRNA CASC11 was upregulated, while plasma miRNA-150 was downregulated in patients with early-stage bladder cancer than in healthy controls. Altered expression of plasma lncRNA CASC11 and miRNA-150 separated patients with bladder cancer from healthy controls. lncRNA CASC11 expression was inversely correlated with miRNA-150 expression in patients with bladder cance but not in healthy controls. Overexpression of lncRNA CASC11 mediated the inhibition of miRNA-150 expression in cancer cells, while miRNA-150 overexpression did not significantly alter lncRNA CASC11 expression. lncRNA CASC11 overexpression promoted, while miRNA-150 overexpression inhibited cancer cell proliferation. miRNA-150 also attenuated the enhancing effects of lncRNA CASC11 overexpression on cancer cell proliferation. However, overexpression of lncRNA CASC11 showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA CASC11 may promote cancer cell proliferation in bladder cancer, and the actions of lncRNA CASC11 are likely through miRNA-150.

Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death.

BACKGROUND/AIMS: SUMOylation is a dynamic process and reversed by the activity of SUMO-specific proteases (SENPs) family. SENP1, a member of this family, is highly expressed and plays oncogenic roles in diverse cancers including prostate cancer. However, the SENP1-transgenic mice exhibit aberrant transformation of the mouse prostate gland but do not develop cancer. Cellular Stress Response 1 (CSR1) is a tumor suppressor gene and frequently deleted in prostate cancers. Overexpression of CSR1 in prostate cancer cells inhibits colony formation, anchorage-independent growth and induces cell death. METHODS: The relationship between CSR1 and SENP1 were determined by immunoprecipitation-based proteomics screen and verified by GST-pull down assay. In vivo SUMOylation assay was used to detect the direct effect of SENP1 in the regulation of CSR1. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Senp1-/- and CSR1-/- PC3 cells. FACS assay was used to determine the apoptosis ratio of cells after transfection. RESULTS: CSR1 is SUMOylated at K582 and rapid ubiquitinated and degradated in prostate cancer cells. SENP1 interacts with and deSUMOylates CSR1 to prevent its degradation and enhances CSR1-dependent prostate cancer cell death. CONCLUSION: Thus, our data indicates that CSR1 is a critical SUMOylated substrate of SENP1 that might partially explain the controversial roles of SENP1 in prostate cancer development.

Characteristics, treatment patterns and retention with extended-release subcutaneous buprenorphine for opioid use disorder: A population-based cohort study in Ontario, Canada.

BACKGROUND: Uptake and retention for opioid agonist treatment (OAT) remains low. Novel extended-release formulations may improve OAT accessibility by reducing the frequency of healthcare visits. Our aim was to examine uptake, characteristics, treatment patterns and retention of individuals initiating extended-release subcutaneous buprenorphine (BUP-ER), a monthly injectable OAT. METHODS: We conducted a population-based cohort study among adults aged 18+ initiated on BUP-ER between February 3, 2020 and March 31, 2022 in Ontario, Canada. Using administrative health data, we defined continuous BUP-ER use based on repeat injections within a 56-day period and used Kaplan-Meier curves to estimate time on treatment. Among new BUP-ER recipients, we described individual and prescriber characteristics, healthcare utilization and treatment patterns. RESULTS: 2366 individuals initiated BUP-ER. The median time to BUP-ER discontinuation was 183 days (interquartile range: 66-428 days) and 52.0% of individuals were co-prescribed buprenorphine/naloxone at least once throughout the period of BUP-ER receipt. Among individuals who initiated on a dose of 300mg BUP-ER and had three or more injections, 18.8% continued to receive only 300mg doses (N=276 of 1470). Furthermore, 28.6% of those whose dose was reduced to 100mg (N=341 of 1194) had a subsequent dose increase to 300mg. CONCLUSIONS: On average, people initiating BUP-ER discontinue within the first 6 months of treatment. While BUP-ER is likely providing an important OAT option, the high occurrence of discontinuation, supplementation with buprenorphine/naloxone, and frequent dose increases suggest inadequacy of current dosing recommendations among a proportion of individuals.

Trends in varying modes of drug use in opioid toxicity deaths in Ontario from 2017 to 2021.

BACKGROUND: Preliminary data indicate a shift toward inhalation instead of injection in opioid toxicity deaths. Understanding changing modes of drug use is essential to addressing the North American drug toxicity crisis driven primarily by unregulated fentanyl. This study aims to comprehensively characterize this shift across Ontario, Canada. METHODS: We conducted a population-based repeated cross-sectional study of accidental opioid toxicity deaths in Ontario from July 1, 2017 to June 30, 2021. For each quarter of the study period, the number and percent of deaths by mode of drug use (inhalation only, injection only, both or other) were reported. Descriptive characteristics were reported in the last two years of the study. RESULTS: There were 6687 accidental opioid toxicity deaths in Ontario over the study period, with a 62.1 % increase in the quarterly number of deaths observed. The prevalence of deaths where inhalation was the only mode of drug use almost doubled, rising from 22.0 % to 43.5 %. There was a corresponding 64.4 % decrease in opioid toxicity deaths with indication of injection alone (29.0 % to 10.3 %). CONCLUSIONS: This study reveals a shift in mode of drug use toward inhalation that is increasingly contributing to opioid toxicity deaths in Ontario. Understanding the shifts in patterns of opioid use serves to provide essential insights into more effective harm reduction and treatment approaches to address the drug toxicity crisis.

USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer. / USH2Açªå˜å’Œå ¶ä»–å ³é”®é©±åŠ¨åŸºå› çªå˜äºšåž‹ä¸Žå ç–«æ£€æŸ¥ç‚¹æŠ‘åˆ¶å‰‚åœ¨è‚ºç™Œæ‚£è€ ä¸­ä¸´åºŠè”ç³»çš„å ³è”ç ”ç©¶.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01|‒|1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49|‒|2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48|‒|1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39|‒|1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32|‒|0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38|‒|0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75|‒|8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88|‒|6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Adherence to antipsychotic laboratory monitoring guidelines in children and youth: a population-based study.

Background: In 2011, the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) published guidelines for the metabolic monitoring of antipsychotic-treated children and youth. Population-based studies examining adherence to these guidelines are needed to ensure the safe use of antipsychotics in children and youth. Methods: We conducted a population-based study of all Ontario residents aged 0 to 24 who were newly dispensed an antipsychotic between April 1, 2018, and March 31, 2019. We estimated prevalence ratios (PRs) and 95% confidence intervals (CI) associating sociodemographic characteristics with the receipt of baseline and follow-up (3- and 6-month) laboratory testing using log-Poisson regression models. Results: Overall, 6,505 of 27,718 (23.5%) children and youth newly dispensed an antipsychotic received at least one guideline-recommended baseline test. Monitoring was more prevalent among individuals aged 10 to 14 years (PR 1.20; 95% CI 1.04 to 1.38), 15 to 19 years (PR 1.60; 95% CI 1.41 to 1.82), and 20 to 24 years (PR 1.71; 95% CI 1.50 to 1.94) compared to children under the age of 10. Baseline monitoring was associated with mental health-related hospitalizations or emergency department visits in the year preceding therapy (PR 1.76; 95% CI 1.65 to 1.87), a prior diagnosis of schizophrenia (PR 1.20; 95% CI 1.14 to 1.26) or diabetes (PR 1.35; 95% CI 1.19 to 1.54), benzodiazepine use (PR 1.13; 95% CI 1.04 to 1.24), and receipt of a prescription from a child and adolescent psychiatrist or developmental pediatrician versus a family physician (PR 1.41; 95% CI 1.34 to 1.48). Conversely, monitoring was less frequent in individuals co-prescribed stimulants (PR 0.83; 95% CI 0.75 to 0.91). The prevalence of any 3- and 6-month follow-up monitoring among children and youth receiving continuous antipsychotic therapy at these time points was 13.0% (1,179 of 9,080) and 11.4% (597 of 5,261), respectively. Correlates of follow-up testing were similar to those of baseline monitoring. Conclusion: Most children initiating antipsychotic therapy do not receive guideline-recommended metabolic laboratory monitoring. Further research is needed to understand reasons for poor guideline adherence and the role of clinician training and collaborative service models in promoting best monitoring practices.

CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study.

This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.

Predictors of pod-type e-cigarette device use among Canadian youth and young adults. / Prédicteurs de l'utilisation de la cigarette électronique à capsule chez les jeunes et les jeunes adultes canadiens.

INTRODUCTION: Changes to federal legislation allowed nicotine-based e-cigarettes legal entry into the Canadian market in 2018. This included pod-type e-cigarettes (pods), such as JUUL, that were later found to be associated with steeply increasing prevalence and greater frequency of e-cigarette use among US and Canadian youth. Multiple studies of risk factors of JUUL use and use initiation have been conducted among various population groups in the US, but little evidence exists pointing to similar risk factors of pod use among Canadian youth and young adults. Understanding these risk factors can inform use prevention and intervention strategies in Canadian and other jurisdictions. METHODS: A total of 668 Canadian youth and young adults recruited by the 2018-19 Youth and Young Adult Panel Study were provided a baseline survey 3 months before and a follow-up survey 9 months after the relaxation of federal nicotine e-cigarette regulations. We used multivariable logistic regression to understand and rank importance of baseline predictors of future pod use among respondents. RESULTS: Past-month cannabis use (OR [odds ratio] = 2.66, 95% CI: 1.66-4.21, p < 0.001), established cigarette use (OR = 3.42, 1.53-7.65, p < 0.01), past cigarette experimentation (OR = 2.40, 1.34-4.31, p < 0.01), having many friends who vaped (OR = 2.15, 1.37-3.34, p < 0.001), age below 18 compared to age over 22 (OR = 5.26, 2.63-10.00, p < 0.001) and male sex (OR = 1.69, 1.16-2.50, p < 0.01) were significant and the most influential predictors of future pod use. CONCLUSION: Similar factors drove pod use among Canadian and US youth and young adults. Appropriate preventive strategies can benefit from considering polysubstance use among high school-aged youth.

Enhanced education for adult patients with persistent post-concussion headaches: a randomized controlled trial.

Aim & Patients: We conducted a randomized clinical trial to determine if an e-learning intervention can enhance recovery in adult patients with persistent post-concussion headaches (PPCH). Materials & Methods: The intervention consisted of three e-learning modules administered at baseline, 6 and 12 weeks. Data were collected on symptoms, community integration, quality of life and healthcare utilization at baseline and 12-week follow-up. ANCOVA was conducted to compare changes. Results: No statistically significant difference was observed on symptoms although we observed a trend toward reduced healthcare utilization and improved quality of life in the intervention group. Conclusion: E-learning modules for patients experiencing PPCH warrant further investigation with data on participant compliance and measures focusing on simpler short-term outcomes.Clinical Trial Registration: NCT03391583 (ClinicalTrials.gov).

Low muscle mass and low muscle strength associate with nonalcoholic fatty liver disease.

BACKGROUND: It is unclear whether low muscle mass and low muscle strength are independently or jointly associated with nonalcoholic fatty liver disease (NAFLD). Hence, the aim of the present study was to investigate the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. METHODS: A total of 5132 participants aged 18-80 years were recruited in this cross-sectional study. NAFLD was diagnosed using ultrasound. Muscle mass was evaluated using skeletal muscle mass index and muscle strength was evaluated using weight-adjusted hand grip strength. Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multivariate logistic regression models were used to explore the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity. RESULTS: Low muscle mass and low muscle strength were positively and independently associated with NAFLD (mass: odds ratio [OR], 2.57; 95% confidence interval [CI], 2.03-3.25; strength: OR, 1.47; 95% CI, 1.21-1.80). Compared with low muscle mass or low muscle strength alone, sarcopenia was associated with a higher risk of NAFLD (OR, 3.91; 95% CI, 2.90-5.28). Whether obesity was defined by body mass index (BMI) or waist circumference (WC), sarcopenic obesity was associated with a higher risk of NAFLD (BMI: OR, 10.42; 95% CI, 7.14-15.22; WC: OR, 11.64; 95% CI, 8.22-16.48) than sarcopenia or obesity alone. CONCLUSIONS: Low muscle mass and low muscle strength were positively and independently associated with NAFLD. When both were presented in the sarcopenic state, the risk of NAFLD was higher, and a concurrence of sarcopenia and obesity showed the highest risk of NAFLD.

Autophagy and Tumor Database: ATdb, a novel database connecting autophagy and tumor.

Autophagy is an essential cellular process that is closely implicated in diverse pathophysiological processes and a variety of human diseases, especially tumors. Autophagy is regarded as not only an anti-cancer process in tumorigenesis but also a pro-tumor process in progression and metastasis according to current research. It means the role of autophagy in tumor is considered to be complex, controversial and context dependent. Hence, a comprehensive database is of great significance to obtain an in-depth understanding of such complex correlations between autophagy and tumor. To achieve this objective, here we developed the Autophagy and Tumor Database (named as ATdb, http://www.bigzju.com/ATdb/#/) to compile the published information concerning autophagy and tumor research. ATdb connected 25 types of tumors with 137 genes required for autophagy-related pathways, containing 219 population filters, 2650 hazard ratio trend plots, 658 interacting microRNAs, 266 interacting long non-coding RNAs, 155 post-translational modifications, 298 DNA methylation records, 331 animal models and 70 clinical trials. ATdb could enable users to search, browse, download and carry out efficient online analysis. For instance, users can make prediction of autophagy gene regulators in a context-dependent manner and in a precise subpopulation and tumor subtypes. Also, it is feasible in ATdb to cluster tumors into distinguished groups based on the gene-related long non-coding RNAs to gain novel insights into their potential functional implications. Thus, ATdb offers a powerful online database for the autophagy community to explore the complex world of autophagy and tumor. Database URL: http://www.bigzju.com/ATdb/#/.

Suppression of autophagy during mitosis via CUL4-RING ubiquitin ligases-mediated WIPI2 polyubiquitination and proteasomal degradation.

Macroautophagy/autophagy is a cellular process in which cytosolic contents are degraded by lysosome in response to various stress conditions. Apart from its role in the maintenance of cellular homeostasis, autophagy also involves in regulation of cell cycle progression under nutrient-deprivation conditions. However, whether and how autophagy is regulated by the cell cycle especially during mitosis remains largely undefined. Here we show that WIPI2/ATG18B (WD repeat domain, phosphoinositide interacting 2), an autophagy-related (ATG) protein that plays a critical role in autophagosome biogenesis, is a direct substrate of CUL4-RING ubiquitin ligases (CRL4s). Upon mitosis induction, CRL4s are activated via neddylation, and recruit WIPI2 via DDB1 (damage specific DNA binding protein 1), leading to polyubiquitination and proteasomal degradation of WIPI2 and suppression of autophagy. The WIPI2 protein level and autophagy during mitosis could be rescued by knockdown of CRL4s or treatment with MLN4924/Pevonedistat, a selective inhibitor of CRLs, via suppression of NAE1 (NEDD8 activating enzyme E1 subunit 1). Moreover, restoration of WIPI2 rescues autophagy during mitosis and leads to mitotic slippage and cell senescence. Our study thus discovers a novel function of CRL4s in autophagy by targeting WIPI2 for polyubiquitination and proteasomal degradation during mitosis. Abbreviations: ACTB, actin beta; ATG, autophagy-related; AMPK, AMP-activated protein kinase; AURKB/ARK2, aurora kinase B; BafA1, bafilomycin A1; CCNB1, cyclin B1; CDK1, cyclin dependent kinase 1; CHX, cycloheximide; CQ, chloroquine; CRL4s, CUL4-RING ubiquitin ligases; DDB1, damage specific DNA binding protein 1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; GST, glutathione S-transferase; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; STK11/LKB1,serine/threonine kinase 11; MTORC1/MTOR complex 1, mechanistic target of rapamycin kinase complex 1; NAE1, NEDD8 activating enzyme E1 subunit 1; NOC, nocodazole; RING, really interesting new gene; RBX1, ring-box 1; SA-GLB1/ß-gal, senescence-associated galactosidase beta 1; TSC2, TSC complex subunit 2; TUBA, tubulin alpha; WIPI2, WD repeat domain, phosphoinositide interacting 2.

Importance of TFEB acetylation in control of its transcriptional activity and lysosomal function in response to histone deacetylase inhibitors.

TFEB (transcription factor EB) is a master regulator of lysosomal biogenesis, function and autophagy. The transcriptional activity of TFEB is mainly controlled by its phosphorylation status mediated by the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) complex 1 (MTORC1). At present, little is known whether other forms of posttranslational modifications (PTMs) such as acetylation also affects is transcriptional activity. In this study, we first observed that a well-established histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) activated lysosomal function in human cancer cells, a process independent of the MTORC1 pathway. Second, SAHA treatment activated TFEB transcriptional activity, as evidenced by increased TFEB luciferase activity and expression of its target genes. Third and more importantly, we observed the enhanced TFEB acetylation in SAHA-treated cells, with identification of 4 acetylation sites. Mutation of these 4 sites markedly diminished TFEB transcriptional activity and lysosomal function induced by SAHA. Finally, we found that TFEB acetylation was functionally implicated in SAHA-mediated autophagy and cell death in cancer cells. Taken together, our results demonstrate that TFEB acetylation is a novel form of PTMs in TFEB that plays an important role in determining its transcriptional activity, lysosomal function and autophagy in cancer cells. ABBREVIATIONS: ACAT1: acetyl-coenzyme A acetyltransferase 1; AHA: L-azidohomoalanine; AO: acidic orange; ATG: autophagy related; CLEAR: Coordinated Lysosomal Expression and Regulation; CQ: chloroquine; CTSB: cathepsin B; HATs: histone acetyltransferases; HDACIs: HDACs inhibitors; HDACs: histone deacetylases; IP: immunoprecipitation; MEFs: mouse embryonic fibroblasts; MS: mass spectrometry; MTOR: mechanistic target of rapamycin (serine/threonine kinase); MTORC1: mechanistic target of rapamycin (serine/threonine kinase) complex 1; PTMs: posttranslational modifications; SAHA: suberoylanilidehydroxamic acid; TFEB: transcription factor EB.

Susceptibility to hepatocellular carcinoma associated with null genotypes of GSTM1 and GSTT1.

AIM:In order to study the association between the null genotypes of GSTM1 and GSTT1 and the genetic susceptibility to hepatocellular carcinoma (HCC).METHODS:The genotypes of GSTM1 and GSTT1 of 63 cases of HCC and 88 controls were detected with the multiple PCR technique.RESULTS:The frequency of GSTM1 null genotype was 57.1% among the cases, and 42.0% among the controls, the difference being statistically significant (X(2) = 3.35, P = 0.067), but X(2) value approaching the significance level. The odds ratio was 1.84 (95% CI = 0.91-3.37). The frequency of GSTT1 non-null genotype was 87.3% among the cases and 62.5% among the controls, the difference being statistically significant (X(2) = 11.42, P = 0.0007274). The odds ratio was 4.13 (95% CI = 1.64-10.70).According to the cross analysis, the GSTT1 non null genotype was more closely associated with HCC than GSTM1 null genotype, and these two factors play an approximate additive interaction in the occurrence of HCC.CONCLUSION:The persons with GSTM1 null genotype and GSTT1 non-null genotype have the increased risk to HCC.