环氧化酶-2基因多态性与回族人群胃癌易感性的关联

目的: 探讨环氧化酶-2(COX-2)-765G>C的单核昔酸多态性与回族人群胃癌易感性的关系.方法: 以PCR-限制性片段长度多态性方法对回族人群中胃癌组( n = 100)、癌前病变组( n =102)和正常对照组( n = 105)进行基因分型. 使用ELISA法检测H pylori感染.结果: COX-2-765GC+CC在胃癌组显著增高( P = 0.021). 交互作用分析显示: 食腌菜的-765GC+CC携带者患胃癌的风险是不食腌菜的-765GG携带者的5.038倍( P = 0.000);H pylori感染阳性的-765GC+CC携带者患胃癌的风险是H pylori感染阴性-765 GG携带者的3.520倍( P = 0.002).结论: COX-2-765G>C和中国甘肃地区回族人群胃癌易感性增高相关. -765 GC+CC分别与食腌菜、H pylori感染在胃癌的发病风险中存在着加乘交互效应.     

环氧化酶-2基因多态性与冠心病易感性的相关性研究

目的探讨环氧化酶-2（COX-2）基因-765G/C多态性与冠心病易感性的关系。方法对226例经冠状动脉造影确诊的冠心病患者和240例正常人进行对照研究。应用聚合酶链反应限制性片断长度多态性技术测定COX-2基因-765G/C多态性。结果COX-2基因-765G/C多态性在冠心病组和正常人群（对照组）中分布的差异有显著性,冠心病组765G等位基因频率明显高于对照组（85.0%比79.4%,P〈0.05）。等位基因频率的相对风险分析发现,G等位基因携带者患冠心病的风险是C等位基因的1.471倍（95%CI：1.044-2.072）。结论COX-2基因启动子-765G/C多态性与冠心病发病具有相关性,其中G等位基因可能是冠心病发病的遗传易感基因。     

环氧合酶-2基因启动子区单核苷酸多态性与非酒精性脂肪肝遗传易感性的关系

目的 通过检测环氧合酶-2(COX-2)基因启动子区单核苷酸的多态性,以探讨其与非酒精性脂肪肝(NAFLD)遗传易感性的关系.方法 对200例NAFLD患者和206名正常对照,采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法对COX-2基因启动子区-765G＞C和-1195G＞A多态性进行基因型分析.计量资料结果用均数±标准差((-x)±s)表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行x2检验.结果 正常对照中,COX-2基因启动子区-765G＞C和-1195G＞A等位基因的分布频率分别为48%和2%,NAFLD患者组二者分别为54%和5%.多变量Logistic回归分析显示:-765GC基因携带者与-765GG基因携带者相比较,前者发生NAFLD的比值比(OR)=2.35 (95% CI为1.17～3.65);-1195AA基因携带者与-1195GG基因携带者相比较,前者发生NAFLD的OR=1.13 (95% CI为1.01～2.46).与单体型G-1195-G765相比较,含有A1195的A-1195-C-765、A1195-G765两种单体型发生NAFLD的相对风险明显升高,OR分别为1.42 (95% CI为1.11～1.63,P＜0.05)和4.24(95% CI为1.72～14.22,P＜0.01).且A-1195-C765发生NAFLD的OR值高于A-1195-G-765、G-1195-C765的单体型.这一结果提示在同一单体型内-1195A与-765C之间存在交互作用.结论 COX-2基因启动子区的-1195G＞A和-765G＞C单核苷酸存在多态性,与NAFLD发生相关,是决定NAFLD个体遗传易感性的重要因素.     

环氧化酶-2与肺癌

环氧化酶-2（ cyclooxygenase-2, COX-2 ）是环氧化酶的诱导型,在肺癌及其转移灶中高表达,以多环节参与肺癌的发生发展,且与肺癌患者的预后有关。COX-2抑制剂的临床应用有预防和抑制肺癌的作用。     

COX-2基因单核苷酸多态性与结直肠腺瘤遗传易感性的关系

目的 探讨环氧合酶-2(COX-2)基因多态性与结直肠腺瘤(CRA)易感性的关系.方法 采用病例对照研究方法,应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)和错配聚合酶链反应-限制性片段长度多态性技术(PIRA-PCR),分别检测110例CRA患者和120名健康人群的COX-2基因-765G＞C、-1195G＞A、8473T＞C 3个多态位点,采用x2检验比较不同基因型与CRA易感性的关系.结果 CRA组和对照组的COX-2-765 G＞C、-1195G＞A 2个位点的3种基因型频率分布差异无统计学意义(P=0.972,P=0.313);两组间COX-2 8473T＞C位点的3种基因型分布差异有统计学意义(P=0.034),Logistic回归分析显示,携带突变等位基因C的个体(8473TC+CC) CRA的易感性显著降低(OR=0.500,95 ％CI:0.274-0.913,P=0.024).结论 COX-2-765G＞C、-1195G＞A可能与CRA易感性无关,COX-2 8473T＞C与CRA易感性相关.     

环氧化酶-2基因-765G>C多态性与老年代谢综合征患者阿司匹林抵抗无关

目的探讨老年代谢综合征患者阿司匹林抵抗的罹患率及其与环氧化酶-2(COX-2)基因-765G>C多态性的关系。方法 106位老年代谢综合征患者口服阿司匹林100mg/d至少20天,根据Chrono-log560CA全血发光血小板聚集系统检测结果分为阿司匹林抵抗(AR)组或阿司匹林敏感(AS)组,然后应用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)技术分析COX-2基因-765G>C多态性。结果老年代谢综合征患者中阿司匹林抵抗的罹患率为31.13%,-765G>C多态性三种基因型GG、GC和CC的分布频率分别为68.9%、22.6%和8.5%,-765C等位基因分布频率为19.8%。AR和AS两组患者-765G>C多态性的基因型(p=0.553)和等位基因(p=0.714)分布频率没有显著差异。结论 COX-2基因-765G>C多态性与老年代谢综合征患者阿司匹林抵抗无关。     

环氧化酶-2与胃癌的研究进展

环氧化酶（COX）-2是花生四烯酸合成前列腺素的限速酶,在胃癌高表达,其表达与炎性因子、肿瘤促进子及幽门螺杆菌感染等多种因素有关。COX-2的高表达通过抑制细胞凋亡、促进新生血管的形成及帮助肿瘤细胞逃逸机体免疫监视等多种作用促进肿瘤的发生及发展。COX-2可以降低肿瘤细胞间的黏附性、促进基底膜的降解及新生淋巴管的形成,促进肿瘤的浸润和转移。COX-2有望成为胃癌治疗的新靶点。     

环氧化酶-2与肺癌

环氧化酶 2 (COX 2 )是内源性前列腺素 (PGs)合成中的限速酶。它通过多种途径参与肺癌的发生、发展和转移 ,并与肺癌患者的预后有关。一些体内外研究表明COX 2抑制剂能够抑制肺癌细胞的生长与转移。临床上选择性COX 2抑制剂有可能成为肺癌预防和化学治疗的新靶点     

COX-2基因多态性与结直肠癌发病风险的关系研究

目的 探讨环氧合酶-2(COX-2)-765G＞C、-1195G＞A、8473T＞C基因多态性与结直肠癌(CRC)遗传易感性的关系,同时评估COX-2基因多态性与某些因素共同作用对CRC发病风险的影响.方法 采用病例对照研究方法,入选CRC患者130例及健康非肿瘤人群120例.PCR-RFLP方法检测病例组和对照组COX-2基因的3个多态基因型,结果采用非条件logistic回归分析,用比值比(OR)及95％可信区间(CI)评估研究因素对疾病危险度的作用.结果 病例组COX-2-765G＞C、-1195G＞A、8473T＞C基因型频率与对照组间的差异均无统计学意义.根据体重指数(BMI)将研究对象分层后,发现-765GG基因型与CRC发病风险的相关性具有统计学意义,与正常BMI(＜23)相比,携带-765GG基因型且超重或肥胖者(BMI≥23)患CRC风险增高(OR=2.024,95％CI:1.089～3.760,P=0.024).此外,还发现吸烟可增加患CRC的风险,与不吸烟人群相比,吸烟人群中的8473TT基因型携带者患CRC的风险明显增高(OR=1.938,95％CI:1.021～3.677,P=0.042).结论 虽然COX-2 765G＞C、-1195G＞A、8473T＞C基因多态性与CRC遗传易感性之间没有相关性,但是携带-765GG基因型的高BMI人群或携带8473TT基因型的吸烟人群的CRC发生风险显著增高.对COX-2基因多态性位点的检测将有助于预防CRC的发生.     

环氧化酶-2与糖尿病

新近研究显示,糖尿病是一种低水平的炎症性疾病.多种因素刺激下,环氧化酶(COX)-2在胰岛及多种组织中高水平表达.它通过与炎症因子和炎症介质如白细胞介素-1、一氧化氮、自由基、前列腺素E等相互作用,对胰岛β细胞产生毒性效应,抑制胰岛素分泌,在糖尿病发生、发展中起重要作用,而且COX-2与糖尿病微血管、神经系统并发症也密切相关.对COX-2的研究可进一步揭示糖尿病发生的分子机制,为预防和治疗糖尿病提供新的思路.     

N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer

AIM:To investigate the possible association between meat intake,cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.METHODS:Patients with CRC were matched for gender and age to healthy controls.Meat intake and cigarette smoking were assessed using a specific frequency questionnaire.DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism.Five NAT2 alle...     

普伐他汀对人结肠癌细胞增殖及COX-2蛋白表达的影响

目的体外观察普伐他汀对人结肠癌细胞HT-29、Ls-174-T细胞增殖、细胞周期及COX-2蛋白表达的影响。方法采用噻唑蓝（MTT）法观察普伐他汀对HT-29和Ls-174-T细胞增殖的影响，流式细胞仪（FCM）研究普伐他汀对细胞周期的作用，免疫细胞化学观察COX-2蛋白的表达。结果体外普伐他汀可抑制HT-29和Ls-174-T细胞增殖，各处理组内G0／G1期细胞增多，但诱导凋亡不明显，体外普伐他汀可减少HT-29和Ls-174-T细胞株COX-2蛋白的表达。结论体外普伐他汀对HT-29和Ls-174-T细胞增殖有抑制作用，该作用可能与使细胞生长阻滞于G0／G1期及抑制COX-2蛋白表达有关。     

COX-1和COX-2在结直肠腺瘤中的表达

目的观察COX-1和COX-2在结直肠腺瘤中的表达情况。方法16例经病理证实的散发性结直肠腺瘤活组织检查标本，15例肠镜检查无明显病变的IBS患者肠黏膜活组织检查标本。免疫组化染色观察COX-1和COX-2表达水平的变化。结果COX-2在结直肠腺瘤组织中的表达异常增高（P〈0．05），而COX-1在正常组织和腺瘤中的表达水平没有明显的变化。结论在结直肠腺瘤组织中，COX-2表达明显升高，提示COX-2参与结直肠腺瘤的发生和发展。     

VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population

Background  The vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in the process of angiogenesis, a crucial phase in tumor growth and metastasis. We carried out a case–control study to evaluate whether polymorphisms of VEGF gene modulate the risk of developing colorectal cancer disease (CCD). Materials and methods  We evaluated VEGF −2578A/C, −460T/C, and +405C/G genotypes obtained from a series of 302 CCD patients and 115 controls from the Italian population using polymerase chain reaction restriction fragment length polymorphism assay. Results  Strong linkage disequilibrium (LD) was detected between −2578A/C and −460T/C (D′ = 0.97; CI = 0.93–1) and between −2578A/C and +405C/G (D′ = 0.97; CI = 0.98–1) in the case group. Complete LD was detected between −2578A/C and +405C/G and between −460T/C and +405C/G (D′ = 1; CI = 0.84–1; CI = 0.82–1, respectively) in the control group. A reduced risk for the disease was associated with −2578C/A and −2578C/C (odds ratio (OR) = 0.34, CI = 0.162–0.676 and OR = 0.38, CI = 0.181–0.775, respectively). A direct association was found for carriers of the VEGF −460C/C polymorphism (OR = 3.55; CI = 1.659–8.469). We identified a protective haplotype −2578A, −460T, and +405G (OR = 0.04; CI = 0.009–0.19) and two different high-risk haplotypes −2578A, −460C, and +405G (OR = 1.90; CI = 1.31–2.27) and −2578C, −460C, and +405C (OR = 9.62; CI = 1.3–70.87). Conclusions  The present study suggests that the VEGF gene polymorphisms may play a role in the development of colorectal cancer. Paolo Maltese and Emanuele Canestrari contributed equally to the study.     

胸苷酸合成酶基因多态性与结直肠癌易感性的关系

目的研究胸苷酸合成酶（thymidylate synthase．TS）基因5＇-非翻译区（untranslated region，UTR）、3＇-UTR多态性及其与饮酒之间的联合作用和结直肠癌（colorectal cancer，CRC）易感性的关系。方法采用病例对照研究（140例病例和343例对照）设计，通过非条件Logistic回归模型和似然比检验分析TS上述多态性及其与饮酒之间的联合作用和CRC易感性之间的关系。结果单独的TS基因多态性与CRC之间无明显联系。两多态性之间联合作用的P值为0．05。无饮酒史者中，＋6bp等位基因是CRC的保护因素（OR=0．57．95％CI．0．32～0．99）．有饮酒史者中，＋6bp等位基因携带者患CRC的风险增加（OR=1．88，95％CI．0．80～4．41），并且随着饮酒年限的延长，OR值逐渐升高。似然比检验提示两者之间存在交互作用（P=0．01）。结论尚不能认为TS基因5LUTR和3LUTR多态性是CRC风险的独立预测因子，两多态性之间、3＇-UTR多态性与饮酒之间存在交互作用，共同改变个体罹患结直肠癌的风险。     

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathoiogic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages Ⅲ-Ⅳand with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages Ⅰ-Ⅱ and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2-positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2-negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.     

X线损伤交叉互补基因1多态性与结直肠癌易感性研究

目的 探讨DNA修复酶X线损伤交叉互补基因1(XRCC1 )外显子三个位点的基因多态性(Arg194Trp 、Arg280His、Arg399Gln)与结直肠癌(CRC)发病风险的关系.方法 以聚合酶链反应和限制性片段长度多态性(PCR-RFLP)分析方法,采用病例-对照研究,对250例CRC患者(病例组,其中结肠癌128例,直肠癌122例)和213名健康人(对照组)的XRCC1基因三个位点的多态性进行了检测,采用SPSS 11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 XRCC1基因194和399二个位点的各基因型频率在两组间分布差异均无统计学意义(P值均>0.05),但病例组XRCC1基因280 Arg/His基因型频率较对照组显著增高(校正后OR=1.66,95%CI:1.01～2.73,P=0.047).在直肠癌患者组中,280Arg/His基因型频率较对照组显著增高(OR=1.82,95%CI:1.02～3.27),携等位基因280His(Arg280His +His280His)的CRC患者的频率显著高于其在对照组中的频率(校正后OR=1.85,95%CI:1.06～3.22),而在结肠癌患者中风险系数相对较低且差异无统计学意义(校正后OR=1.31,95%CI:0.74～2.35).结论 XRCC1 Arg194Trp和 Arg399Gln基因多态性与结肠癌易感性无关,但280Arg/His基因型能增加CRC易感性,等位基因280His是直肠癌风险因素.

Abstract：

Objective To investigate the correlation between three gene locus polymorphisms of X-ray repair cross-complementary protein 1 (XRCC1) exon (Arg194Trp, Arg280His and Arg399Gln) and the risk of colorectal cancer (CRC). Methods A case-control study was performed in 250 CRC patients (case group, 128 colon cancer patients and 122 rectal cancer patients) and 213 healthy individuals (control group). The three gene locus polymorphism of XRCC1 was tested by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotype distribution and allele frequency of each locus was analyzed with SPSS 10.0 software. Results There was no significant difference in allele frequency of XRCC1 at 194 and 399 loci (P > 0.05). However, the 280 Arg/His allele frequency of XRCC1 was higher in case group than that in control group (OR=1.66,95%CI:1.01~2.73,P=0.047). The 280Arg/His allele frequency was higher in rectal cancer group than that in control group (OR =1.82,95%CI:1.02~3.27). The frequency of 280His allele (Arg280His and His280His) was higher in case group than that in control group (OR=1.85,95%CI:1.06~3.22). However, it was a relative low risk factor of colon cancer and there was no significant difference between colon cancer group and control group (OR=1.85, 95%CI:1.06~3.22). Conclusions There was no correlation between XRCC1 Arg194Trp and Arg399Gln polymorpohisms and the risk of CRC. However, 280Arg/His genotype may increase the risk of CRC, and 280His allele is a risk factor of rectal cancer.