p53基因突变在胃癌发生中的作用

胃癌的发生发展是多基因参与、多步骤进行的过程。而p53基因突变作为一种重要抑癌基因失活方式，在其中发挥了重要作用。现综述近年来在胃癌中发现的p53基因突变类型、方式、地区差异性及与多种因素之间的关系等方面研究进展。     

食管癌组织中Rb基因突变与表达的研究

应用ＰＣＲ直接顺序和Ｎｏｒｔｈｅｒｎ ｂｌｏｔ杂交方法，分析了食管癌组织中Ｒｂ基因的突变和表达状况。应用ＰＣＲ扩增Ｒｂ基因片段，发现５％（１／２０）的食管癌有Ｒｂ基因１７和２１外显子缺失；１／６的食管癌旁组织中，有Ｒｂ基因１７外显子缺失；还发现甲基苄基亚硝胺（ＮＭＢｚＡ）诱发的人胎儿食管癌有Ｒｂ基因１７和２１外显子缺失。ＰＣＲ直接测序，发现４０％（４／１０）癌组织中有Ｒｂ基因的突变，首次证实食管癌     

HBV—DNA基因型与肝癌的预测性相关研究

HBV-DNA 基因型与肝癌发生的预测性相关研究为山东医科大学承担的山东省科委研究课题。本课题从分子水平上首次系统地对乙肝、肝癌患者的血清、淋巴细胞、肝癌/肝组织内 HBV-DNA 存在状态分布、定位及其复制活性等特点进行了系统分析研究,现报道如下:     

Ⅱ相毒物代谢酶基因、致癌物代谢及与大肠癌遗传易感性研究近况

 据生物转化反应的类型,毒物代谢酶相应分为Ⅰ相代谢酶和Ⅱ相代谢酶。Ⅰ相代谢酶主要有细胞色素P450 (CYP) 超家族; Ⅱ相代谢酶主要有谷胱甘肽S-转移酶( GST) 、N-乙酰化转移酶(NAT ) 、尿苷二磷酸葡萄糖醛酸转移酶(UGT ) 、环氧化物水解酶( EH)等。体内的致癌物一般先由Ⅰ相代谢酶氧化、还原、水解等作用,改变毒物的功能基团,使其降解或转变为亲电团而具致癌作用; Ⅱ相代谢酶则催化毒物或Ⅰ相代谢酶的代谢产物与其极性基团结合,增加其水溶性,利于排出体外,或被活化为亲电子致突变剂或致癌剂。毒物代谢酶对致癌物的代谢反应及其多 态性在大肠癌(CRC) 的发生、发展过程中起重要作用。     

原发性肝癌组织p53和ASPP2基因突变检测及临床意义

目的:检测原发性肝癌组织中p53与ASPP2基因突变,并探讨其临床意义.方法:收集24例肝癌标本,分别提取DNA及RNA,PCR扩增p53基因,逆转录PCR扩增ASPP2基因并进行半定量分析,基因测序后进行突变分析.结果:24例肝癌患者中,p53基因在肝癌组织中的突变率是75.0%,在癌旁组织中的突变率为20.8%,P<0.01;肝癌组织中ASPP2与GAPDH的灰度比值平均为0.81,癌旁组织中为0.85,P>0.05,但是癌组织和癌旁组织均未检测到ASPP2基因突变.结论:在原发性肝癌发生过程中,p53基因突变比ASPP2基因突变可能起到更重要的作用.     

广西扶绥县肝癌高危人群 HBV S 区基因突变与原发性肝癌的相关性研究

目的　探讨广西扶绥县肝癌高危人群乙型肝炎病毒（hepatitis B virus,HBV）S区基因突变及其与原发性肝癌（primary liver cancer,PLC）的关系。方法 收集来自扶绥县肝癌高危人群队列30例原发性肝癌患者为病例组,同时在队列中按条件收集30例未发生肝癌的持续HBsAg阳性者为对照组,两组1∶1匹配,收集血清标本。采用巢式PCR方法扩增出HBV S区基因片段,对扩增产物进行测序分析。结果 病例组和对照组突变率差异有统计学意义的突变点为T140A、T140C、T300C、G620A（P＜0.05）;条件logistic回归分析显示,T140C突变可能降低原发性肝癌发病风险（OR=0.484,95%CI：0.239~0.994）,T300C突变可能增加原发性肝癌发病风险（OR=2.911,95%CI：1.110~7.629）。结论 与原发性肝癌发生相关的HBV S区基因突变位点有T140A、T140C、T300C和G620A,其中T140C、T300C与原发性肝癌发生有独立相关性。     

膀胱癌相关基因的研究进展

膀胱癌在中国为最常见的泌尿系统肿瘤。膀胱癌的发生发展是一个多步骤的过程,异常基因型的长期积累导致恶性表型的出现。与膀胱癌相关的基因主要有癌基因（如H-ras、FGFR3、erbB2、CCND1、mdm2等）、抑癌基因（如INK4A/ARF、Rb、TP53、PTEN、TSC1、PTCH、DBCCR1等）及DNA错配修复基因等。本文就与膀胱癌相关的几类主要基因的研究进展作一综述。     

肺癌易感性相关基因研究进展

综述了与肺癌易感性有关的 3种基因 :细胞色素氧化酶p4 5 0 (cytochromep4 5 0 ,CYPs)基因、谷胱苷肽硫基转移酶 (glutathioneS transferase ,GSTs)基因以及DNA修复酶基因的多态性与肺癌的易感性之间的关系 ,并且也简要介绍了以上 3种酶基因多态与DNA加合物以及DNA加合物与p5 3和ras基因突变关系的研究现状。     

肝细胞癌p53基因突变初步研究

本文应用快速银染多了矣酶链反应单链构像多态（ＰＣＲ－ＳＳＣＰ）方法检测了３０例肝细胞癌（ＨＣＣ）组织中ｐ５３基因变异情况。结果１３例癌组织中有异常电带，其中２闰于第５外显子，各有３例位于第６和第７外显子，位于第８显子有５例，ｐ５３基因变异的病例乙型肝炎表面抗原均阳性，实验结果表明：本技术能有效检测出基因突变；肝细胞癌中ｐ53基因突变率较高且有多个位点；肝细胞癌ｐ５３基因突变可能与乙型肝炎病毒感染有关     

MBD4基因的单核苷酸多态与肝细胞肝癌遗传易感性研究

目的：探索DNA损伤修复基因hMBD4的遗传多态Glu346Lys与肝细胞癌（hepatocellular carcinoma，HCC）易感性的关系。方法：对96例原发性HCC患者和96例对照外周血DNA进行测序分型。结果：我们发现正常人群Glu／Glu、Glu／Lys、Lys／Lys基因型频率分别为40．4％、46．8％和12．8％，HCC组为41.7％、48．8％和9．5％。等住基因Lys频率在病例和对照分别为33．9％和36．2％，两组比较差异无统计学意义，P〉0．05。结论：DNA修复基因hMBD4的Lys等位基因可能与HCC的遗传易感性无关。     

睾丸生殖细胞肿瘤遗传易感性研究进展

睾丸生殖细胞肿瘤是严重危害青壮年男性身体健康的疾病,目前其病因尚未探明;睾丸生殖细胞肿瘤发病年龄较早、没有明确环境致癌因素、存在明显种族发病差异、有较高遗传度;因此从人群肿瘤遗传易感性角度着手研究,更有助于探究发现其病因,为筛查、诊断、预防及治疗提供依据.利用基于单核苷酸多态性的全基因组关联研究等研究方法,近来国外发现了多个睾丸生殖细胞肿瘤发病相关基因,使睾丸生殖细胞肿瘤的遗传易感性研究取得了重要的进展.     

胃癌患病风险基因研究进展

胃癌是我国常见的恶性肿瘤,其致病因素涉及环境及遗传等多种因素的相互作用。本文对胃癌患病风险有关的代谢酶相关基因、解毒酶基因、免疫相关基因、DNA修复基因、原癌基因及抑癌基因的研究进展作一综述。     

代谢酶基因多态性与子宫内膜癌易感性关系的研究进展

 子宫内膜癌(Endometrial Cancer，简称EC)是女性生殖器官三大恶性肿瘤之一，占女性生殖系统恶性肿瘤的20％～30％。虽然子宫内膜癌在我国的发病率一直低于西方国家，但是自二十世纪六十年代以来，上海市区子宫内膜癌发病率逐年上升，且发病年龄有年轻化的趋势；目前子宫内膜癌已超出宫颈癌位居女性肿瘤发病的第十位。     

DNA修复基因hOGG1多态与肺癌遗传易感性

背景与目的 :研究修复8_羟基鸟嘌呤的hOGG1基因Ser326Cys多态与中国人肺癌易感性的关系。 材料与方法 :采用病例_对照分子流行病学方法 ,以PCR_限制性片段多态(Restrictionfragmentlengthpolymorphism,RFLP)技术 ,对128名正常对照和124例肺癌患者hOGG1基因第326位点Ser/Cys多态性进行分析 ,并比较不同基因型与肺癌发病危险的关系。 结果: 对照组和肺癌组人群的Cys等位基因频率基本相同(37.5 %和39.9 %) ,但肺癌组的Cys/Cys基因型频率为19.4 % ,高于对照组的10.2 %。与携带Ser/Ser或Ser/Cys基因型者比较 ,携带Cys/Cys基因型个体患肺癌的危险约增加1倍(OR^ =2.12 ,95 %CI=1.03～4.39)。 结论: hOGG1基因Ser326Cys多态可能与中国人肺癌易感性相关 ,可以作为肺癌遗传易感性标志物 ,用于易感个体的预警和预防。     

Genetic Variation in PDCD6 and Susceptibility to Lung Cancer

Lung cancer is the most common type of cancer and one of the leading causes of death in the world. Geneticfactors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein6, may function as a tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80% tonewly histologically diagnosed lung cancer patients. To explore the relationship between PDCD6 and NSCLC,we examined two single nucleotide polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region)of the PDCD6gene.A hospital-based case-control study was carried out including 302 unrelated NSCLC patientsand 306 healthy unrelated subjects. Significantly increased NSCLC risk was found to be associated with the Tallele of rs4957014 (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of rs3756712did not shown any significant difference between NSCLC group and controls (P=0.327, OR=0.879, 95%CI=0.679-1.137). In conclusion, we firstly demonstrated the association between the PDCD6 gene and risk of NSCLC ina Chinese Han population.     

OGG1 rs1052133 Polymorphism and Genetic Susceptibility to Chronic Myelogenous Leukaemia

Background: In some cancer cells, the OGG1 gene is somatically mutated and highly populated. This study wasconducted to examine whether OGG1 rs1052133 polymorphism is associated with the genetic background of chronicmyelogenous leukaemia (CML) in Sudan. Methods: A total of 332 CML patients and 70 healthy controls were includedin this study. Overall, the genotypes (P=0.0000) and allele (C vs. G, P=0.0007) differed considerably in the frequenciesof OGG1 rs1052133 polymorphism between CML patients and controls. Our study is the first to evaluate the associationof polymorphism with CML risk with OGG1 rs1052133. Results: A statistically significant association was observedbetween the genotype distribution of OGG1 rs1052133 polymorphism and CML (P=0.0000) patients. A similar resultwas also observed in the allele distribution (C vs. G, P=0.0007) compared with healthy controls when comparedOGG1 rs1052133 genotypes with CML stages. Results: Genotype and allele frequencies of OGG1 rs1052133 amongCML patients. A statistically significant association was observed between the genotype distribution of the OGG1rs1052133 polymorphism and CML patients (P=0.0000). A similar result was also observed in the allele distribution(C vs. G, P=0.0007) compared with healthy controls with stages of CML in OGG1 rs1052133 genotypes. Conclusion:The results suggest that single nucleotide polymorphism in the gene involved in the restoration of DNA base excision(OGG1 rs1052133) can play a key role in the risk of appearance of CML. To clarify the role of OGG1 in the geneticbasis of CML, further case control with larger sample sizes and fine-mapping is required.     

代谢酶基因多态性与食管癌易感性关系的研究进展

目前关于食管癌易感性的研究已成为食管癌分子流行病学的研究热点,文章对其中研究较多的几种代谢酶基因的概况及与食管癌易感性的关系进行了综述.     

NQO1基因多态性与膀胱癌易感性的关系

[目的]探讨浙江地区依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶1(NQO1)基因多态性与膀胱癌易感性的关系.[方法]采用病例对照研究方法,应用相对的两对引物—聚合酶链反应技术(PCR-CTPP),对99例膀胱癌患者和100例非肿瘤患者的NQO1 C609T基因型进行检测,并分析其与膀胱癌易感性的关系.[结果]NQO1 C609T基因型分布频率在膀胱癌组和对照组之间的差异具有统计学意义(P＜0.05),携带609TT基因型的个体罹患膀胱癌的风险是携带609CC基因型个体的2.448倍(95％CI为1.125～5.326).NQO1 C609T基因型分布频率在膀胱癌不同病理分级和临床分期之间的差异均无统计学意义(P＞0.05).[结论]NQO1 C609T基因多态性可能与膀胱癌的易感性相关,携带NQO1 609TT基因型的人群易患膀胱癌.     

Genetic Heterogeneity in Breast Cancer Susceptibility

Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.