肝癌患者及正常人群中黑色素瘤相关抗原1的基因多态性

目的 研究黑色素瘤相关抗原1(MAGE-1)在中国肝癌患者中的表达，并阐明MAGE-1基因变异是肿瘤细胞内的突变还是单核苷酸多态性(SNP)，以及基因变异在人群中的分布状况。方法 提取19例原发性肝癌(HCC)患者的癌组织、癌旁组织总RNA，用逆转录-多聚合酶链反应(RTPCR)方法检测组织MAGE-1基因mRNA的表达，并通过PCR产物测序分析编码基因是否存在变异；提取HCC患者癌组织、癌旁组织和外周血细胞基因组DNA，以及23例正常献血员外周血细胞基因组DNA，分析MAGE-1编码基因的变异状况并利用软件对变异抗原蛋白的生物学意义进行了初步探讨。结果 癌组织中MAGE-1表达阳性率为47．4％(9／19)，癌旁组织无表达。序列测定显示，MAGE-1 cDNA编码基因存在3种类型：一类是Ⅰ型(GenBank M77481)，发生率为11．1％(1／9)；另一类型(C159T，A272G，G393A)发生率为55．6％(5／9)，称之为TGA型，导致编码的2个氨基酸的改变分别是T32A和R72Q；第三种类型(A272G，C991T，A1125G)发生率为33．3％(3／9)，仅A272G引起一个氨基酸的替换(T32A)，称之为GTG型。经对基因组DNA分析，证实以上3种基因类型不是肝癌组织的基因突变，而是SNP，其在肝癌患者和正常献血员中分布的比例分别为：Ⅰ型占26．3％(5／19)和60．9％(14／23)；TGA型占57．9％(11／19)和47．8％(11／23)，GTG型占21．1％(4／19)和21．7％(5／23)。TGA型和GTG型的序列已被GenBank收录，编号为AF463515和AY148486。在男性研究对象中，SNP型别在是否患有HCC及是否表达MAGE1抗原的患者中的分布差异均无显著性。SNP可能产生多个新的能与人白细胞抗原结合的抗原表位。利用多个模块从头搭建的方法，得到Ⅰ型和TGA型的蛋白三维空间结构模型。结论 MAGE-1在HCC患者的癌组织中表达，发现MAGE-1存在3种高频分布的SNP类型，尝试建立了MAGE-1蛋白的三维空间模型，这为进一步研究不同的MAGEI-1抗原性肽疫苗奠定了基础。     

乙型肝炎病毒X区基因变异与原发性肝癌的关系研究

目的初步研究乙型肝炎病毒(HBV)X区基因变异与原发性肝癌的关系。方法收集39例HBV感染患者的肝(癌)石蜡组织标本,其中慢性乙型肝炎(CHB)14例、肝细胞癌(HCC)25例。采用聚合酶链式反应(PCR)方法扩增组织中HBV X区基因,并对PCR产物进行DNA测序,分析常见变异位点的变异情况。结果 1.HCC组与CHB组相比,在X区发生插入/缺失变异,联合变异的位点及例数增多,并且A1762T与G1764A常发生双突变。2.HBV X区变异频率较高位点依次是C1655T/G、A1605C/G、A1762T、G1764A、A1772B、A1645C、C1687A、G1776T。结论 HBV X区存在点突变、插入/缺失变异及联合变异,可能在HCC的发生和发展过程中起重要作用。     

MAGE-A1、MAGE-C2及SSX-1在原发性肝细胞癌中的表达及意义

目的 检测肿瘤-睾丸抗原(CT抗原)MAGE-A1、MAGE-C2和SSX-1 mRNA在原发性肝细胞癌(HCC)中的表达情况.方法 采用RT-PCR方法检测MAGE-A1、MAGE-C2和SSX-1 mRNA在55例HCC患者癌及癌旁组织中的表达,对产物进行测序,并对检测结果与临床指标进行分析.结果 55例HCC患者的癌组织中,MAGE-A1、MAGE-C2和SSX-1 mRNA的表达率分别为60.0%、14.5%和40.0%;癌旁组织无表达.结论 CT抗原MAGE-A1、MAGE-C2和SSX-1 mRNA在HCC中呈高表达,是HCC免疫治疗的理想靶位.     

HBV基因型及A1762T/G1764A双位点变异在肝癌患者中的临床意义

目的:研究肝细胞癌(HCC)患者乙型肝炎病毒(HBV)基因型与基本核心启动子(BCP)基因区A1762T/G1764A双位点变异(BCP区双突变)之间的关系,探讨HCC的发病机制。方法:选择40例HCC患者作为研究组,40例慢性乙型肝炎(CHB)患者作为对照组,采用多对型特异性引物PCR扩增法进行基因分型及HBV基因多态性芯片检测BCP区A1762T/G1764A双位点变异。结果:40例HCC患者中有30例HBV DNA定量阳性,平均对数值为(6·53±1·31)copy/ml,将30例HBV DNA定量阳性的HCC及40例CHB患者的血清进行HBV基因分型及基因变异检测,结果显示30例HCC中HBV B基因型5例(16·7%),C基因型25例(83·3%);BCP区双突变共有20例(67·7%),其中B基因型1例,C基因型19例,BCP双突变率在B基因型和C基因型中分别为20%(1/5)和76%(19/25);40例CHB患者中B基因型32例(80%),C基因型8例(20%);BCP区双突变共有13例,其中B基因型8例,C基因型5例,BCP双突率在B基因型和C基因型中分别是25%(8/32)和62·5%(5/8)。结论:肝细胞癌的发生与BCP区A1762T/G1764A双位点变异有关,多发生在HBV C基因型的患者。     

MAGE-4基因在肝细胞肝癌中的表达及临床意义

目的通过研究MAGE-4基因在肝细胞肝癌组织中的表达,并与患者临床资料进行分析,探讨 MAGE-4基因与肝细胞肝癌(HCC)患者临床指标及转移与复发的关系,为MAGE-4基因编码蛋白用于HCC患者免疫治疗提供依据. 方法用RT-PCR的方法对31例HCC患者癌组织及相应癌旁组织MAGE-4基因表达进行测定,对全部RT-PCR扩增产物中目的基因片段进行DNA测序以证实其为 MAGE-4基因,患者均测定并统计AFP、AFU、抗HCV、HBsAg、AFP mRNA、肿瘤直径等临床指标. 结果 31例HCC患者肝癌组织中MAGE-4基因表达的阳性率38.7% (12/31)明显高于癌旁组织中MAGE-4基因表达的阳性率0% (0/31),P＜0.01.HCC患者肝癌组织中MAGE-4基因表达的阳性率与患者AFP、AFU、抗HCV、HBV标志物、AFP mRNA、肿瘤直径等临床指标均无关,P＞0.05. 结论 MAGE-4基因在HCC患者肝癌组织中特异高表达,可能作为HCC患者免疫治疗攻击的靶点,HCC患者肝癌组织中 MAGE-4基因表达的阳性率与HCC患者肿瘤标志物、转移、复发均无关.     

乙型肝炎病毒基因型、BCP及PC区变异与拉米夫定治疗后HBV DNA反弹的关系

目的:探讨HBV基因型、C区基本核心启动子(BcP)及前C(PC)区变异与拉米夫定抗病毒治疗后HBV DNA反弹的关系.方法:应用多引物对巢式PCR法,PCR-序列分析法,检测拉米夫定治疗27例乙型肝炎患者(治疗组),以及19例从未用过抗病毒治疗患者(对照组)的HBV基因型PC区,BCP的突变位点.结果:27例HBV DNA反弹的患者9例检出G1896A变异率高于对照组(33.33% vs 5.26%,P<0.05),4例检出C1856T变异(14.81%).治疗组4份治疗前标本未检出G1896A、C1856T和BCP变异.与对照组比较,治疗组PC(G1896A)及BCP(A1762T G1764A)双变异的患者中B基因型的构成比增高,分别为75%和50%,C基因型的构成比下降,分别为25%和50%.其中在BCP(A1762T G1764A)变异患者中B、C基因型构成比与对照组比较有显著性差异(P<0.05).4例HBV DNA反弹患者治疗前未检出有基因变异,治疗后有2例检出变异,BCP变异1例,BCP PC变异1例.27例HBV DNA反弹患者BCP变异4例,PC变异2例,BCP PC变异8例.结论:BCP(T1762/A1764)变异、PC区(G1896A)变异可能与拉米夫定治疗后HBV DNA反弹有关.病毒变异导致的HBV DNA反弹可以是单基因变异引起,也可以是多个基因联合变异引起,拉米夫定治疗后B基因型患者更易发生A1762T G1764A变异.     

mtDNA Cyt-b、 ATPase6在浸润性乳腺癌中的突变及意义

目的 检测线粒体DNA (mtDNA) Cyt-b、ATPase6在浸润性乳腺癌组织和癌旁组织的突变情况,寻找特异性位点.方法 采用PCR结合基因测序方法,对延边朝鲜族地区浸润性乳腺癌患者(30例)的癌组织及癌旁组织进行mtDNA Cyt-b、ATPase6基因测序,对照人线粒体DNA剑桥修定序列,分析其突变情况.结果 在研究对象的乳腺癌mtDNA中共发现Cyt-b基因区有6个高突变发生率位点,即A15326G、C14766T、G15301A、G15043A、T14783C、C15402T,其中A15326G、C14766T突变率最高;而ATPase6基因区共发现3个高突变发生率位点,即C8673T、A8729G、T8955C,其中C8673T、A8729G突变率最高.结论 mtDNA Cyt-b、mtDNA ATPase6高突变发生位点可为浸润性乳腺癌的诊断及乳腺癌细胞线粒体功能评价提供有价值的参考.     

原发性肝癌C-kit和SCF基因的表达及意义

探讨C -kit、SCF基因编码的蛋白在肝癌(HCC)组织中的表达及其临床病理意义。采用免疫组化SP法检测92例肝癌中C -kit、SCF蛋白表达,同时取对应的癌旁肝组织及30例良性肝病组织作对照。结果显示,HCC中有较强的C -kit和SCF蛋白表达,癌旁组织呈弱表达,良性肝病组织则呈阴性表达。C -kit、SCF阳性率肝癌组织与癌旁组织、良性肝病组织比较差异有非常显著意义(P均<0 . 0 1)。C -kit、SCF蛋白表达与AFP异常、肝癌分级、门脉癌栓有关。C -kit、SCF蛋白过表达可能在原发性肝癌的发生、发展中发挥作用。     

肝细胞癌患者IL-18基因-137G/C和-607A/C位点单核苷酸多态性变化及其意义探讨

目的探讨肝细胞癌(HCC)患者白细胞介素-18(IL-18)基因-137G/C和-607A/C位点单核苷酸多态性(SNP)的变化。方法在178例伴有HBV感染的HCC患者和251例健康人,取外周静脉血提取DNA,采用聚合酶链反应-连接酶检测反应(PCR-LDR)行基因分型,测定IL-18基因-137G/C和-607A/C位点SNP。结果 HCC患者和健康人IL-18-37 G/C基因GG基因型、GC基因型和CC基因型分布频率分别为75.3%对47.0%(P0.05)、20.8%对51.4%(P0.05)和3.9%对1.6%(P0.05),G等位基因和C等位基因分布频率分别为93.6%对72.7%(P0.05)和6.4%对27.3%(P0.05);HCC患者和健康人IL-18-607A/C位点AA基因型、AC基因型和CC基因型分布频率分别为37.6%对13.5%(P0.05)、43.3%对66.9%(P0.05)和19.1%对19.5%(P0.05),A等位基因和C等位基因分布频率分别59.3%对47.0%(P0.05)和40.7%对53.0%(P0.05);HCC组IL-18-137G/C位点的GG基因和G等位基因频率显著高于健康人(P0.05),HCC组IL-18-607A/C位点的AA基因和A等位基因频率也显著高于健康人(P0.05),提示携带IL-18-137G/C和IL-18-607A/C位点基因型和A等位基因者罹患HCC的风险增加。结论携带IL-18基因-137G/C位点GG基因型和G等位基因以及-607A/C位点AA基因型和A等位基因者可能更容易发生HCC,对HBV感染者筛查这些基因可能有助于早期发现肝肿瘤,以利于早期处理和改善预后。     

p73基因在肝细胞癌中的表达及其临床意义

背景:p73基因是新发现的一种抑癌基因,其在肿瘤发生、发展中的作用尚不明确.目的:探讨p73基因在肝细胞癌中的表达、突变程度及其与临床预后的关系.方法:采用定量逆转录聚合酶链反应(RT-PCR)检测35例肝细胞癌和配对癌旁组织,以及10例转移淋巴结和10例正常淋巴结组织中p73基因的表达;采用内含子PCR产物StyⅠ酶切分析法调查标本的杂合性;采用PCR-单链构象多态性(SSCP)检测p73基因的突变情况.结果:35例肝细胞癌组织中有26例p73 mRNA呈高表达,癌旁组织则呈低表达,两者表达率有显著差异(P＜0.01);20例中高分化癌组织中有13例p73 mRNA呈中高表达,15例低分化癌组织中有13例p73 mRNA呈中高表达,两者阳性率之间有显著差异(P＜0.01);18例Ⅰ～Ⅱ期肝细胞癌标本中有9例p73 mRNA呈中高表达,17例Ⅲ～Ⅳ期肝细胞癌标本中p73 mRNA均呈中高表达,两者阳性率之间有显著差异(P＜0.05).10例转移淋巴结组织中p73 mRNA均呈高表达,而10例正常淋巴结组织中均呈低表达,两者之间有显著差异(P＜0.01).12例杂合性肝细胞癌组织标本中,有10例p73基因存在G/C:A/T双等位基因表达,在癌旁组织中则均为G/C表达,未见A/T表达.肝细胞癌和癌旁组织中未见p73基因突变.结论:p73基因的表达与肝细胞癌的分化程度、临床分期和预后有关,突变可能不是p73基因起作用的主要方式.     

Mutation analysis of novel human liver-related putative tumor suppressor gene in hepatocellular carcinoma

AIM: To find the point mutations meaningful for inactivation of liver-related putative tumor suppressor gene (LPTS) gene, a human novel liver-related putative tumor suppressor gene and telomerase inhibitor in hepatocellular carcinoma. METHODS: The entire coding sequence of LPTS gene was examined for mutations by single strand conformation polymorphism (SSCP) assay and PCR products direct sequencing in 56 liver cancer cell lines, 7 ovarian cancer and 7 head neck tumor cell lines and 70 pairs of HCC tissues samples. The cDNA fragment coding for the most frequent mutant protein was subcloned into GST fusion expression vector. The product was expressed in E.coli and purified by glutathione-agarose column. Telomeric repeat amplification protocol (TRAP) assays were performed to study the effect of point mutation to telomerase inhibitory activity. RESULTS: SSCP gels showed the abnormal shifting bands and DNA sequencing found that there were 5 different mutations and/or polymorphisms in 12 tumor cell lines located at exon2, exon5 and exon7. The main alterations were A(778)A/G and A(880)T in exon7. The change in site of 778 could not be found in HCC tissue samples, while the mutation in position 880 was seen in 7 (10 %) cases. The mutation in the site of 880 had no effect on telomerase inhibitory activity. CONCLUSION: Alterations identified in this study are polymorphisms of LPTS gene. LPTS mutations occur in HCC but are infrequent and of little effect on the telomerase inhibitory function of the protein. Epigenetics, such as methylation, acetylation, may play the key role in inactivation of LPTS.     

SOCS3 Genetic Polymorphism Is Associated With Clinical Features and Prognosis of Hepatocellular Carcinoma Patients Receiving Hepatectomy

Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown.A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined.Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier.Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment.     

Association between epidermal growth factor 61A/G polymorphism and hepatocellular carcinoma susceptibility in Chinese patients

Background and aims: Chronic hepatitis B virus (HBV) infection is an important risk factor for hepatocellular carcinoma (HCC) development in China, while little is known of the genetic susceptibility to hepatocarcinogenesis. The epidermal growth factor (EGF) pathway plays an important role in tumorigenesis, including HCC. EGF polymorphisms are associated with susceptibility to several types of cancers. Therefore, this study aimed to assess whether EGF genetic polymorphisms can influence HCC development. Methods: A total of 338 chronic HBV‐infected patients (186 HCC patients and 152 cirrhotic patients) and 186 healthy individuals were enrolled in this study. EGF 61A/G polymorphisms of all subjects and 12 cell lines were assayed with polymerase chain reaction‐restriction fragment length polymorphism and the sequencing method. Furthermore, EGF protein levels were measured in the serum and the results were compared with the different genotypes. EGF expression in the liver tissue of the HCC patients was detected by immunohistochemical analysis. Results: EGF 61A and 61G allele frequencies in healthy subjects were 28.76 and 71.24%. EGF 61GG and G allele frequencies in the HCC group were higher than those in the cirrhosis group. EGF protein levels with the GG genotype were significantly higher than those with either the GA or the AA genotype. About 59.09% of HCC liver tumour tissues assayed showed EGF protein expression. Conclusions: The EGF 61 GG genotype might be associated with a high risk for the development of chronic HBV infection‐related HCC in Chinese patients.     

Cytokine gene polymorphisms in Japanese patients with hepatitis B virus infection--association between TGF-beta1 polymorphisms and hepatocellular carcinoma

BACKGROUND/AIMS: In this study, we determined the frequencies of the genotypes associated with the polymorphism of the cytokines genes, and investigated their association with the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers. METHODS: Genetic polymorphism in the cytokines TNF-alpha, IFN-gamma, TGF-beta1, IL-6, and IL-10 were studied in 236 Japanese patients with HBV infection. The genetic polymorphisms of these cytokines were analyzed by polymerase chain reaction-sequence-specific primer (SSP). RESULTS: There was no statistically significant difference in the genetic polymorphisms of TNF-alpha, IFN-gamma, and IL-10 genes between HBV carriers with HCC and those without HCC. However, the TGF-beta1+29 (codon 10) C/C genotype was lower in HBV carriers with HCC than in those without HCC (HCC 14.6% vs non-HCC 31.9%). The association of HCC was significantly lower in HBV carriers with C/C genotype than in those with T/C or T/T genotype in position +29 of the TGF-beta1 gene. CONCLUSIONS: Our findings suggest that the genetic polymorphism in codon 10 of the TGF-beta1 gene may play a role in HCC development in patients with chronic HBV infection.     

Interleukin-10 promoter polymorphisms in patients with hepatitis B virus infection or hepatocellular carcinoma in Chinese Han ethnic population

BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study. METHODS: The polymorphisms of IL-10 promoter region were detected by pulymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way. RESULTS: Polyrnorphisms of T/C or T/N on-872 site occurred frequently in Han ethnic population. Pulyrnorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the pulymorphisms was inserting base A between-1058 and-1057. CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.     

环氧化酶与阿司匹林疗效的相关性研究

目的探讨环氧化酶(cyclooxygenase,COX)基因型及其表达与阿司匹林疗效的相关性。方法选择老年高血压患者181例,根据血栓弹力图分为阿司匹林敏感(aspirin sensitive group,AS)组106例,非阿司匹林敏感(notaspirin sensitive group,NAS)组75例;PCR产物直接测序分析法检测COX-1(A-842G,C22T,C50T,G128A,C644A,C714A)和COX-2(G765C)基因型;实时定量PCR及Western blot法,检测患者外周血细胞中COX-1和COX-2 mRNA及蛋白表达水平。结果 NAS组与AS组COX-1(G128A,C644A)位点突变型等位基因分布差异无统计学意义(P>0.05);与AS组比较,NAS组COX-2(G765C)位点突变型等位基因频率更高(P<0.01);而COX-1(A-842G,C22T,C50T,C714A)位点在检测人群中未发现突变型等位基因。NAS组COX-2 mRNA和蛋白表达明显高于AS组(P<0.05)。结论调查人群中COX-2(G765C)位点多态性可能与阿司匹林抵抗的发生具有相关性;COX-2表达可能是导致阿司匹林抵抗发生的原因之一。     

肝细胞癌抑癌基因p53突变

目的分析重庆地区肝细胞癌ｐ５３基因突变谱．方法住院肝细胞癌患者２０例，皆经病理证实，长期在重庆地区居住，其中早期小肝癌４例，中期６例，晚期１０例．采用ＰＣＲ－ＳＳＣＰ，ＰＣＲ直接测序技术分析ｐ５３基因５，６，７和８外显子突变．结果ｐ５３基因总的突变率为４０％．其中外显子５和６各占１０％，外显子７占２０％，未发现外显子８的突变；测序证实外显子７为第２４９位密码子Ｇ→Ｔ的颠换突变．突变病例多为晚期肿瘤．结论重庆地区肝细胞癌存在明显的ｐ５３基因突变，反映了该地区肝癌与黄曲霉毒素和ＨＢＶ或ＨＣＶ病毒有关     

Impact of interleukin-1beta genetic polymorphisms on the development of hepatitis C virus-related hepatocellular carcinoma in Japan

To examine the effects of polymorphisms in the gene encoding proinflammatory interleukin (IL)-1beta in patients infected with hepatitis C virus (HCV) in Japan, we studied 364 patients with chronic HCV infection (146 of whom had hepatocellular carcinoma [HCC] and 218 of whom did not) and 230 healthy control subjects. IL-1B-511 and IL-1RN genotypes were ascertained, and IL-1B-511 genotype T/T was found to be significant risk factors for the development of HCC, indicating that polymorphism in the IL-1B-511 genetic locus is one of the possible determinants of progression of hepatitis C to HCC.     

Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.