细胞周期蛋白D1基因多态与人结直肠癌遗传易感性

目的探讨细胞周期蛋白D1(Cyclin D1)基因第870位点单核苷酸多态(G870A)与结直肠癌(colorectal cancer,CRC)遗传易感性的关系。方法采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)方法,检测345例CRC与670名对照的G870A基因型分布及差异。结果CRC和对照两组人群的Cyclin D1 G870A基因型分布差异无统计学意义(P>0.05)。与GG基因型相比,GA、AA基因型及A等位基因携带者(GA及AA基因型)的CRC风险分别为1.08倍(95%CI=0.75～1.54)、1.01倍(95%CI=0.68～1.51)及1.06倍(95%CI=0.75～1.49)。经性别、年龄、肿瘤位置、组织学分化程度和Dukes分期等因素分层分析,结果均显示G870A与CRC发病风险无显著性相关。结论Cyclin D1 G870A多态与宁波地区人群的CRC发病风险无相关性。     

基因多态与胃癌遗传易感性的关系

基因多态性是一组由遗传决定的性状,它们已显示在中间水平上影响疾病的遗传易患性。胃癌是由环境因素和遗传因素共同引发的恶性肿瘤,研究发现许多基因多态与胃癌的遗传易感性有关。本将就与胃癌遗传易感性有关的几个功能基因的多态性作一综述。     

基因多态与胃癌遗传易感性的关系

基因多态性是一组由遗传决定的性状 ,它们已显示在中间水平上影响疾病的遗传易患性。胃癌是由环境因素和遗传因素共同引发的恶性肿瘤 ,研究发现许多基因多态与胃癌的遗传易感性有关。本文将就与胃癌遗传易感性有关的几个功能基因的多态性作一综述     

毒物代谢酶基因多态与肝癌遗传易感性研究进展

肝癌是我国最常见的恶性肿瘤之一，其发生是一个十分复杂的生物学过程，是遗传因素和环境因素相互作用的结果。暴露在相同的环境因素下，只有很少一部分人患肝癌的事实表明：个体是否患肝癌并非单纯取决于环境因素，在很大程度上还取决于个体的遗传易感性。毒物代谢酶的遗...     

GSTM1基因内三核苷酸重复序列长度多态与肝癌遗传易感性…

为探讨谷胱甘肽－Ｓ－转移酶Ｍ１基因５＇端非编码区ＣＧＧ三核苷酸重复序列长度多态与肝癌遗传易感性的关系，采用ＰＣＲ－ＰＡＵＧＥ－ＤＮＡ银染方法，对６５例肝癌患者和１０６例健康对照的研究表明，病例组和对照组ＣＧＧ拷贝数小于６者，分别占４９．２３％和７．５５％，两组差异显著（Ｐ〈０．０００１）。ＯＲ值为１１．８８，ＥＦ值为０．４５０９。提示ＣＧＧ拷贝数小于６者，患肝癌的危险性增加１０．８８倍，由ＣＧＧ拷     

N—乙酰化转移酶基因多态与肝癌遗传易感性的研究

为探讨Ｎ－乙酰化转移酶（ＮＡＴ）基因多态与肝癌遗传易感性的关系，应用ＰＣＲ、ＡＳＰＣＲ和ＲＦＬＰ，对６５例肝癌患者和１０６例健康对照进行了研究。结果表明，病例组慢型基因频率为７０．７７％，对照组为５２．８３％，两者差异显著（Ｐ＝０．００１）。ＯＲ值为２．１６，ＥＦ值为０．３８０１。提示携带慢型基因者患肝癌的危险性增加１．１６倍，由慢型基因所致的肝癌病例占人群中全部肝癌病例的３８．０１％。病例组基因型Ｆ１／Ｆ１、Ｆ１／Ｓ和Ｓ／Ｓ的频率分别为９．２３％、４０．００％和５０．７７％，对照组则分别为２２．６４％、４９．０６％和２８．３０％，两者差异显著（Ｐ＝０．００５６）。ＯＲ值分别为１．００、２．００和４．４０，存在剂量反应关系。发现４个新的慢型基因亚型，其点突变组合为３４１／５９０、５９０／８０３、２８２／３４１／５９０、２８２／３４１，将其暂命名为Ｓ９，Ｓ１０，Ｓ１１和Ｓ１２。     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

TP53基因多态与结直肠癌肝转移遗传易感性的相关性

目的 探讨TP53基因C-8343G、C-1863T及第72密码子(R72P)单核苷酸多态性与结直肠癌(colorectal cancer,CRC)肝转移风险的关系.方法 采用TaqMan和聚合酶链反应-限制性片段长度多态性方法,检测121例伴肝转移CRC与性别、年龄匹配的280例不伴肝转移CRC的各单核苷酸多态性的基因型分布及差异.结果 C-8343G和C-1863T基因型分布在伴和不伴肝转移的两组CRC人群间差异均无统计学意义.R72P增加CRC肝转移的发生风险:与PP基因型相比,RP基因型、RR基因型和R等位基因携带者(RP或RR基因型)的肝转移风险分别增加至2.21倍(95%CI:1.13～4.33)、2.26倍(95%CI:1.03～4.94)和2.22倍(95%CI:1.16～4.26).CRC组织中P53表达状态的分层分析结果显示:对于P53表达阳性者,72R携带者的肝转移风险与PP基因型相比进一步增加至3.28倍(95%CI:1.21～8.88);而对于P53表达阴性者,PP基因型与72R携带者的肝转移风险差异无统计学意义(比值比为1.37,95%CI:0.52～3.62).结论 TP53增加CRC,特别是P53表达阳性CRC的肝转移风险,可作为CRC肝转移高危人群的筛选指标;C-8343G和C-1863T可能均与CRC肝转移风险无关.     

mTORC1基因多态性位点与中国新疆散发性结直肠癌发病风险的关联性北大核心CSCD

目的筛查及分析PI3K/AKT/mTOR信号转导通路中mTORC1基因多态性位点与结直肠癌发病风险的相关性及其临床意义。方法收集2000年至2013年间新疆医科大学第一附属医院665例原发性结直肠癌患者和695名健康对照,通过病例－对照研究,运用Logistic回归分析mTORC1相关基因中10个多态位点（mTOR：rs1034528,rs2295080;Raptor：rs1062935,rs3751934;mLST8：rs3160,rs26865;DEPTOR：rs2271900,rs4871827;AKT1S1：rs2290774,rs2353005）与结直肠癌易感性的关系。结果mTORC1相关基因与结直肠癌发病风险相关,并与人群的年龄、性别、吸烟状态及体重指数相关。其中,mLST8 rs26865 AA基因型在≤68岁（OR＝0.64,95%CI＝0.43-0.96,P＝0.031）、女性（OR＝0.61,95%CI＝0.38-0.99,P＝0.046）、无吸烟人群（OR＝0.55,95%CI＝0.35-0.87,P＝0.010）中均能降低结直肠癌的发病风险;mTOR rs1034528 CC基因型在〉68岁的人群中提高了结直肠癌的发病风险（OR＝3.34,95%CI＝1.12-9.91,P＝0.030）、Raptor rs3751934 CA/AA基因型在体重指数〉25 kg/m^2的人群中能降低结直肠癌的发病风险（OR＝0.68,95%CI＝0.47-0.98,P＝0.038）、AKT1S1 rs2290774 CC基因型在不吸烟的人群中能降低结直肠癌的发病风险（OR＝0.67,95%CI＝0.45-0.99,P＝0.048）。mTORC1低风险基因型叠加与结直肠癌发病风险相关性分析结果显示,同时携带两个以上低风险基因型的人群要比没有或只携带1个低风险基因型的人群患结直肠癌的风险要低（OR＝0.74,95%CI＝0.58-0.95,P＝0.017）,这在≤68岁、男性、体重指数〉25 kg/m^2及不吸烟人群中尤其明显。mLST8 rs26865基因型与mLST8及下游蛋白4EBP1和p70S6K的表达无相关性。结论mTORC1相关基因多态位点与中国新疆散发性结直肠癌的发生具有一定的相关性,但相关效应较低,尚需在大样本量的、多中心、不同种族的结直肠癌研究中加以验证。     

HER-2基因Ile655Val多态性与结直肠癌易感性分析

目的 探讨HER-2原癌基因Ile655Val多态性与结直肠癌易感性的相关性,及其在自然人群中的分布频率.方法 应用病例对照研究,对浙江省嘉善县292例结直肠癌患者和842名健康对照者采用聚合酶链反应-限制性片段长度多态性方法检测HER-2基因密码子655基因型.结果 结直肠癌组HER-2基因Ile/Val+Val/Val基因型频率(25.34%)和Val等位基因频率(13.36%)均显著高于对照组(18.41%和9.74%)(P<0.05).与Ile/lie基因型携带者相比,Ile/Val+Val/Val基因型携带者患结直肠癌的风险增加(OR=1.54,95%CI:1.11～2.14).HER-2基因多态性与吸烟、饮酒的交互作用OR值分别为1.43(95%CI:0.88～2.30)和1.29(95%CI:0.73～2.29).结论 HER-2基因Ile655Val多态性与结直肠癌易感性相关,但是这种多态性与吸烟、饮酒在结直肠癌发生中不存在交互作用.     

CDH1基因-160(C→A) 多态与福建地区中国人群胃癌遗传易感性的关联研究

目的 上皮钙黏着蛋白（E—cadherin）的编码基因CDHI是重要的肿瘤抑制基因，本研究探讨CDH1基因-160（C→A）多态性在福建地区胃癌人群中的分布及其与福建地区胃癌发病风险的相关性。方法 采用聚合酶链反应-变性高效液相色谱分析方法对102例胃癌患者和101名正常对照者进行CDH1基因-160（C→A）多态的基因型分析，比较基因型分布和发病风险的关系；危险度OR及95％CI应用非条件Logistic回归分析计算。结果 CDH1基因-160（C→A）多态的CC、CA、AA基因型在病例组中的分印频率分别为58（56．9％）．38（37．3％），6（5．9％）；在对照组的分布频率分别为55（54．5％），41（40．6％），5（5％）；两组间分布的差异无统计学意义（P〉0．05）。AA基因型没有显著性地提高或降低胃癌的发病危险（OR=1．12；95％CI：0．32～3．95）；携带A等化基因与胃癌的临床病理特征也无关联性。结论 CDH1基因-160（C→A）多态性可能与福建地区中国人群胃癌发生的遗传易感性无关。     

Over-expression of RALYL suppresses the progression of ovarian clear cell carcinoma through inhibiting MAPK and CDH1 signaling pathways

Background: The molecular mechanism in the progression of ovarian clear cell carcinoma (OCCC) remains unclear.Objective: This study aimed to investigate the potential function of RAYLY in OCCC.Methods: To validate RAYLY expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in OCCC tissues and the cell lines of OCCC and epithelial ovarian carcinoma (EOC). Subsequently, the biological effects of RALYL were evaluated through colony formation, and cell proliferation, migration and invasion assays. Finally, RNA-sequencing and gene set enrichment analysis (GSEA) were conducted to explore potential mechanism of RALYL in OCCC.Results: In our study, RALYL was significantly down-regulated in a majority of OCCC tissues compared to adjacent non-tumorous tissues, and OCCC cells had a lower expression level of RALYL than that of EOC cells. OCCC patients with high RALYL expression had a better pathological stage and prognosis. In vitro, over-expression of RALYL inhibited cell proliferation, migration and invasion in OCCC. GSEA analysis and western blot indicated an enrichment of MAPK and CDH1 signaling pathways in OCCC cells without RALYL over-expression.Conclusions: RALYL played an important role in the progression of OCCC, and might serve as a potential prognostic biomarker and novel therapeutic target for OCCC.     

遗传性弥漫型胃癌家系上皮型钙黏素基因的分析

 摘要：目的 研究在遗传性弥漫型胃癌家系中是否存在上皮型钙黏素基因(CDH1)以及基因表达的异常。 方法 收集符合遗传性弥漫型胃癌(HDGC)诊断标准的1个家系中15例成员的外周血和组织标本。通过免疫组化和Western blot 的方法检测组织标本CDH1蛋白表达; 提取基因组DNA, 通过PCR扩增DNA直接测序检测CDH1基因16个外显子突变。用克隆测序法,鉴定CDH1基因启动子区CpG位点甲基化状况。 结果 先证者和另一胃癌患者(家系2号成员)的癌旁胃粘膜上皮细胞CDH1蛋白表达较正常胃粘膜减弱, 两者肿瘤组织的蛋白表达几乎为阴性。包括先证者在内的11例家系成员第14外显子mRNA水平2377位点存在一个C?T的单核苷酸多态性(single nucleotide polymorphism, SNP), 但未检测到16个外显子的胚系突变。相对于正常胃粘膜, 先证者和家系2号成员的胃癌组织均有CDH1基因启动子的高甲基化, 其瘤旁粘膜也有高甲基化。结论 此HDGC家系中,CDH1基因表达丢失可能和胃癌发生有关, CDH1基因外显子突变不是其肿瘤组织上皮型钙黏素蛋白表达丢失的直接原因, 基因启动子区的甲基化可能是导致其失活的原因之一。     

CDH1‐related blepharocheilodontic syndrome is associated with diffuse gastric cancer risk

We report the first case of diffuse gastric cancer in an individual with familial blepharocheilodontic syndrome (BCD) due to a germline CDH1 likely pathogenic variant. To date, other BCD affected relatives are nonpenetrant for diffuse gastric cancer posing challenges to counseling regarding gastric and breast cancer surveillance, and preventative total gastrectomy.     

De novo CDH1 mutation in a family presenting with early-onset diffuse gastric cancer

In this report, we describe the first concluded case of a de novo germline mutation in CDH1 in a hereditary diffuse gastric cancer (HDGC) kindred. The incident case was a woman with a personal history of Hodgkin's lymphoma and diffuse gastric cancer, who was then confirmed to have a CDH1 mutation (c.1792 C>T (R598X)). The patient's mother was found to have the same CDH1 germline mutation; however, neither maternal grandparent was found to carry the mutation, thus leading to a conclusion that the proband's mother's mutation is of de novo origin. This case highlights the importance of recognition of the HDGC syndrome and of testing for CDH1 germline mutations in young individuals with diffuse gastric cancer without a family history of the disease.     

The E-cadherin (CDH1)--160 C/A polymorphism and prostate cancer risk: a meta-analysis

Published data on the association between E-cadherin (CDH1) -160 C/A polymorphism and prostate cancer (PCA) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A logistic regression approach proposed for molecular association studies was used to estimate a biological model of the gene effect. A total of 11 studies including 2637 cases and 2673 controls were involved in this meta-analysis. Logistic regression analysis indicated that the CDH1 -160 C/A genotypes were associated with PCA risk. The genetic model test indicated that the genetic model was most likely to be dominant (CA+AA vs CC). Overall, meta-analysis indicated that the -160A allele carriers (CA+AA) had a 21% elevated risk of PCA, when compared with the homozygotes (CC) (odds ratio (OR)=1.21; 95% confidence interval (CI): 0.97-1.51; P=0.090, P(heterogeneity)=0.001). In the subgroup analyses by ethnicity, significantly elevated risks were associated with -160 variant genotypes (CA+AA) in both European and Asian populations (OR=1.24; 95% CI: 1.08-1.43; P=0.003, P(heterogeneity)=0.220 and OR=1.54; 95% CI: 1.23-1.93; P<0.001, P(heterogeneity)=0.200). However, no significant associations were found in Africans (OR=0.59; 95% CI: 0.32-1.09; P=0.090, P(heterogeneity)=0.070). Although some modest bias could not be eliminated, this meta-analysis suggests that the CDH1 -160A allele is a low-penetrant risk factor for developing PCA, especially in Europeans and Asians.     

The role of PRDM1 gene polymorphism in the progression of hepatocellular carcinoma in Egyptian patients

In Egypt, hepatocellular carcinoma (HCC) ranks as the second largest cause of cancer mortality. PRDM1 is a tumor suppressor gene essential for the differentiation and regulation activity of plasma cells and T cells. It plays a vital role in T cell exhaustion of chronic viral infection and HCC. We aimed to study the role of PRDM1 gene polymorphism in HCV and HCC-related to hepatitis C virus (HCV) progress in Egyptians. The case-control study included 300 Egyptian patients divided into 100 HCC,100 cirrhosis, and 100 control. Laboratory investigations were done for some clinicopathological biomarkers, including liver function tests, complete blood picture, serum alpha-fetoprotein, and hepatitis markers (HBsAg, anti-HCV-Ab). TaqMan allelic discrimination assay technique was used to genotype PRDM1 gene polymorphism. Multivariant analysis (logistic regression) assessed the association between the polymorphisms with HCC progression and designed the suggested model for HCC prediction. The frequencies of the G allele and GG phenotype in the control group were significantly more than that of the HCC and cirrhosis group. However, GA genotypes and A allele frequencies significantly increased in the HCC patients than in cirrhosis and controls. In addition, by comparing the HCC group and the non-HCC group (controls and cirrhotic patients), the subjects carrying AA or GA have 2 times more risk to develop HCC than those carrying GG genotypes (odd ratio = 2.045% and 95% confidence interval are (1.123−3.722) p = 0.019). Multivariate analysis results suggested a model of Aspartate transaminase (AST), Albumin, and PRDM1 polymorphism to predict the risk of HCC in Egyptians. In addition, PRDM1 polymorphism has an association with HCC prognosis (tumor size). For PRDM1 polymorphism, the A allele and AA might be considered as HCC-related to the HCV risk factor. In addition, AST, Albumin, and PRDM1 polymorphism predict the risk of HCC in Egyptians Therefore, the polymorphism might help in identifying the susceptible Egyptians to HCC. In addition, polymorphism might have a role in HCC prognosis.