COX-2基因多态性及H pylori感染与胃癌高发区甘肃河西地区胃癌的相关性

目的:研究COX-2-899G>C,COX-2codon 587G>A基因多态性在胃癌高发区甘肃河西地区健康人群与胃癌患者的分布,检测幽门螺旋杆(Hpylori)在上述人群中的感染情况,探讨COX-2-899G>C,COX-2codon587G>A基因多态性以及H pylori感染与河西地区胃癌发生的关系.方法:采用PCR-TaqMan探针法检测甘肃河西地区健康人群和胃癌患者COX-2-899G>C,COX-2codon 587G>A的基因多态性,用Warhin-starry染色法检测本研究对象的Hpylori感染率.结果:COX-2-899G>C分为G/G,G/C,C/C三种基因型,其频率在胃癌患者中分别为72.9％,21.4％,5.7％;在普通人群中分别为84.0％,12.8％,3.2％.与G/G基因型相比,COX-2-899*C基因携带者患胃癌的风险增加(OR=1.956,95％CI:1.067-3.586).COX-2codon587G>A三种基因型为G/G,G/A,A/A,其频率在胃癌患者中分别为86.4％,11.4％,2.2％;在健康人群中分别为89.6％,9.6％,0.8％.COX-2eodon 587G>A三种基因型在胃癌组和健康对照组间无显著性差别.Hpylori感染率在胃癌组和对照组分别为68.6％,50.4％,两组间具有显著差异(P=0.003).分层分析提示COX-2-899*C基因携带者若同时伴有Hpylori感染,其患胃癌的风险明显增加(OR=2.471,95％CI:1.076-5.675).结论:COX-2-899G>C的C等位基因增加我国胃癌高发区甘肃河西地区胃癌发病的风险,而且与H pylori感染对胃癌的发病有一定的协同作用;Cox-2 codon 587G>A基因多态性与甘肃河西地区胃癌的易感性无关.     

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。     

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.     

PARP-1基因多态性与胃癌易感性的关系

目的:探讨聚腺苷二磷酸核糖聚合酶-1(PARP-1)Val762Ala,Lys940Arg基因多态性与甘肃省地区汉族人群胃癌易感性的关系.方法:采用多重单碱基延伸SNP分型技术(Multiplex SNaPshot)对甘肃省胃癌高发区河西地区汉族人群中经病理确诊的原发性胃癌150例,健康对照组152例进行PARP-1基因2个SNP位点基因分型.使用ELISA法检测H.pylori感染.结果:发现PARP.1 940Lys/Arg基因型分布在胃癌组明显高于对照组(OR=2.917,95%CI:1.430-5.947.P=0.002);PARP-1762 Val/Ala基因型分布在胃癌组明显高于对照组(OR=1.685.95%CI:1.040-2.729,P=0.034).分层分析显示,在吸烟人群中,PARP-1 940Lys/Arg基因型携带者患胃癌的风险是Lys/Lys型携带者的8.430倍(OR=8.340;95%CI:2.664-26.144,P=0.000);在饮酒人群中,PARP-1 940Lys/Arg基因型携带者患胃癌的风险是Lys/Lys型携带者的3.333倍(OR=3.333,95%CI:1.214-9.155,P=0.015),在H.pylori感染阳性人群中,PARP-1 762A1a/Ala基因型携带者患胃癌的风险是Val/Val携带者的2.360倍(OR=2.360.95%CI:1.256-4.433,P=0.007).同时携带PARP-1 940 Lys/Arg和PARP-1 762Ala/Ala+Val/Ala基因型的个体患胃癌的发病风险是PARP-1 940Lys/Lys和PARP-1 762Val/Val基因型携带者的4.2倍(OR=4.200,95%CI:1.430-12.338.P=0.006).结论:PARP-1 940Lys/Arg和PARP-1 762Ala/Ala或Ala/Ala基因型与中国甘肃地区汉族人群胃癌发病风险增高相关;PARP-1 Lys940Arg 与吸烟,饮酒,PARP-1 Val762Ala与H.pylori感染以及PARP-1 Lys940Arg与PARP-1 Val762Ala在胃癌的发病风险中都各自存在着加乘交互效应.     

云南哈尼族彝族幽门螺杆菌感染人群胃癌易感基因研究

胃癌的发生是生物、环境、宿主等因素共同作用的结果．宿主遗传因素与幽门螺杆菌（H．pylori）感染后的不同临床结局有关。目的：筛选云南红河州哈尼族彝族Hpylori感染人群的胃癌易感基因,探讨不同基因型和等位基因与H．pylori感染宿主胃癌发病风险的相关性。方法：通过PubMed、CNKI和HapMap数据筛选出12个中国人群胃癌易感相关单核苷酸多态性（SNP）位点,以芯片技术对哈尼族彝族H．pylori感染慢性胃炎和胃癌患者的这些SNP位点进行分型。结果：IL-1β-3IC／T和IL-1β-511C/T位点存在完全连锁不平衡．其基因型（P=0．014）和等位基因频率（P=0．049）在胃癌和胃炎组中有显著差异,-511CT／-31CT（OR=2．256,95％CI：1．048～4．855）和-511TT/-31CC（OR=3．312,95％CI：1．462～7．502）基因型胃癌发病风险显著高于-511CC／-31TT基因型。COX-2．899C／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．033）,GG基因型胃癌发病风险显著高于CG基因型（OR=2．796,95％CI：1．053～7．423）。TNF—α-238A／G位点基因型频率在胃癌和胃炎组中有显著差异（P=0．037）．AA、AG基因型胃癌发病风险显著高于GG基因型（OR=2．600．95％CI：1．130～5．985）。结论：IL-1β-31C、IL-1β-511T等位基因和COX-2—899GG基因型可增高云南红河州哈尼族彝族Hpylori感染人群的胃癌发病风险,TNF-α-238GG基因型对上述人群的胃癌发生具有保护作用。     

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.     

P53Arg72Pro多态性及H pylori感染与胃癌高发区甘肃河西地区胃癌的关系

目的:检测H pylori在甘肃河西地区健康人群与胃癌患者中的感染,并探讨P53Arg72Pro基因多态性以及H pylori感染与胃癌高发区甘肃河西地区胃癌发生的关系.方法:采用PCR-TaqMan探针法检测甘肃河西地区健康人群和胃癌患者P53Arg72Pro的基因多态性,用Warhin-starry染色法检测本研究对象的H pylori感染率.结果:H pylori感染率在胃癌组和对照组分别为68.6%,50.4%,H pylori感染率在两组间具有显著差异(OR=2.147,95%CI:1.302-3.541);P53Arg72Pro分为Arg/Arg,Arg/Pro,Pro/Pro3 种基因型,其频率在胃癌患者中分别为15.7%,60.0%,24.3%;在健康人群中分别为25.6%,54.4%,20.0%.与Arg/Arg基因型相比,Arg/Pro或Pro/Pro单独频率在2组间差异无统计学意义,但P53Pro等位基因(Arg/Pro+Pro/Pro)携带者在胃癌者和对照组间差异有统计学意义(OR=1.846;95%CI:1.006-3.387).分层分析提示H pylori阳性感染者或吸烟人群,若其同时携带有P53Pro等位基因,他们患胃癌的风险明显增加.结论:P53Arg72Pro位点基因多态性与我国胃癌高发区甘肃河西地区胃癌发病的风险相关,P53Pro等位基因与H pylori感染或吸烟因素有一定的协同作用.     

XPG基因多态性与胃癌发病风险研究

目的评价XPG His1104Asp和XPG His46His基因多态性与胃癌发病风险的相关性。方法纳入咸宁市中心医院2008年1月-2010年10月218例新发胃癌患者和218例无肿瘤病史的健康对照者。采用聚合酶反应-限制性片段长度多态性分析方法进行XPG His1104Asp和XPG His46His的基因分型,采用酶联免疫吸附法(ELISA)测定患者的幽门螺杆菌(Helicobacter pylori,H.pylori)感染情况。结果携带XPG 1104GG基因型的研究对象患胃癌的风险显著增加,调整后的OR(95%CI)为1.82(1.03~3.34)。携带XPG 1104CG和GG基因型的H.pylori阳性感染者患胃癌的风险显著高于携带CC基因型,OR(95%CI)分别为1.53(1.05~2.16)和2.16(1.37~3.75),XPG His46His基因多态性与胃癌发生无相关性。结论携带XPG 1104GG基因多态性能够增加胃癌发病的风险,该研究结果有助于评价健康人群患胃癌的风险,能够筛选出高危人群并及早进行预防。     

环氧化酶2基因多态性与急性冠状动脉综合征的关联研究

目的探讨环氧化酶2(COX-2)基因-1195G>A和-765G>C位点与中国汉族人群急性冠状动脉综合征(ACS)的相关性。方法选择ACS患者250例(ACS组),同期选取健康体检者266例(对照组)。采用扩增阻碍突变系统结合TaqMan探针的实时荧光定量PCR方法对COX-2基因多态性位点(-1195G>A和-765G>C)进行基因分型。多因素logistic回归分析各多态性位点与ACS的相关性。结果在男性中,ACS组-1195G>A基因型及等位基因频率与对照组比较,差异有统计学意义(GG:23.4%vs 33.8%,GA:50.6%vs 49.4%,AA:25.5%vs 16.9%,P=0.049;G:48.7%vs 58.4%,A:51.3%vs 41.6%,P=0.014);与-1195G>A位点GG基因型比较,AA+GA基因型发生ACS的风险更高(P=0.042),行多因素分析校正相关危险因素后,差异有统计学意义(OR=1.971,95%CI:1.130³.438,P=0.017)。在女性中,ACS组-1195G>A位点基因型及等位基因频率与对照组比较,差异无统计学意义(P>0.05)。单体型分析提示,在男性中,ACS组A-1195-765-G频率显著高于对照组,差异有统计学意义(P=0.012),而在女性中,ACS组A-1195-765-G频率差异无统计学意义(P>0.05)。结论在中国汉族人群中,COX-2基因-1195G>A基因多态性以及单体型A-1195-765-G与男性ACS有关,与女性无关。     

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.     

COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

白细胞介素-6与胃癌易感性的相关研究

目的评价IL-6 174G/C和IL-6 572G/C基因多态性与胃癌风险的相关关系,以及IL-6基因多态性与幽门螺杆菌(H.pylori)感染和吸烟的交互作用。方法采用病例对照研究方法,纳入咸宁市中心医院消化内科2008年1月-2011年5月新发胃癌246例,非肿瘤患者274例作为对照组。采用PCR-RFLP方法测定IL-6 174G/C和IL-6 572G/C的基因分型。结果研究发现携带IL-6 174CC基因型和C等位基因型胃癌发病风险显著增高,调整后的OR(95%CI)分别为1.88(1.07~3.48)和1.56(1.14~2.52)。携带IL-6 174GC和CC基因型在H.pylori阳性感染者中和吸烟者中均能增加患胃癌的风险,IL-6 174G/C基因多态性与H.pylori感染有交互作用(P0.05)。研究未发现IL-6 572G/C基因多态性与胃癌发病风险有相关关系。结论本研究结果表明IL-6基因多态性具有促进胃癌发生和发展的作用,IL-6可以作为胃癌遗传学的检测指标,用于检验胃癌易感个体的生物学指标。     

The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea

Background/Aims

The potential role of the cyclooxygenase (COX)-2 polymorphism has been reported in relation to the risk of gastrointestinal tract malignancies. Therefore, we investigated whether COX-2 polymorphisms are associated with the risk of gastric cancer (GC) in Korea, one of the areas with a high prevalence of this condition.

Methods

We evaluated the genotypic frequencies of COX-2-765 and -1195 in 100 peptic ulcer patients, 100 GC patients, and 100 healthy controls. The polymorphisms of the COX-2-765 and -1195 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphisms.

Results

The frequencies of the COX-2-1195 GG, GA, and AA genotype were 20%, 60%, and 20% in intestinal-type GC and 8%, 48%, and 44% in diffuse-type GC, respectively (p=0.021). There were no significant differences in the frequency of COX-2-765 genotypes between intestinal-type GC and diffuse-type GC (p=0.603). Age- and sex-adjusted logistic regression analysis showed that the COX-2-1195 AA genotype was the independent risk factor of diffuse-type GC compared with the COX-2-1195 GG genotype (p=0.041; odds ratio, 6.22; 95% confidence interval, 1.077 to 35.870).

Conclusions

The COX-2-1195 AA genotype may render subjects more susceptible to diffuse-type GC.     

Polymorphism of -765G 〉 C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection：A study from northern India

AIM： To investigate -765G 〉 C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease （PUD） and nonulcer dyspepsia （NUD）. METHODS： We enrolled 348 adult patients （62 gastric adenocarcinoma, 45 PUD and 241 NUD） undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests （RUT, culture, histopathology and PCR） were positive. Genotyping for -765G 〉 C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS： Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P 〈 0.001, odds ratio （OR） 8.20; 95% confidence interval （95% CI）, 4.08-16.47] and PUD （77.4% vs 31.1%, P 〈 0.001; OR 8.04; 95% CI, 3.25-19.90）. Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with （OR 7.83; 95% CI 3.09-19.85） and without H pylori infection （OR 7.06; 95% CI, 2.61-19.09）. Patients with C carrier and H pylori infection had significant risk for the development of PUD （P 〈 0.001; OR 5.65; 95% CI, 2.07-15.34）. CONCLUSION： -765G 〉 C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.     

Host TNF-alpha-1031 and -863 promoter single nucleotide polymorphisms determine the risk of benign ulceration after H. pylori infection

OBJECTIVES: This study tested whether host genotypes of the tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphism (SNP) could determine clinical and histological outcomes after Helicobacter pylori infection. METHODS: A total of 524 dyspeptic patients, 424 with and 100 without H. pylori infection, were checked for TNF-alpha promoter SNP over the locus on -1031(T/C), -863(C/A), -857(C/T), -806(C/T), and -308(G/A) by sequence-specific oligonucleotide probe. Each patient received panendoscopy to take gastric biopsy to detect H. pylori infection and its related histology using the updated Sydney's system. Gastric TNF-alpha expressions were stained by immunohistochemistry. RESULTS: In H. pylori-infected patients, -1031C or -863A carriers of TNF-alpha promoter had more severe gastric neutrophil infiltration and TNF-alpha gastric staining than individuals with -1031TT or -863CC genotype, respectively (p<0.05). The multivariate logistic regression verified both -1031C and -863A carriers were independent risk factors to have duodenal ulcers and gastric ulcer without IM in the H. pylori-infected hosts (p<0.05). As compared to -863CC and -1031TT genotype combinations, the ulcer risk after H. pylori infection was 2.46 (95% CI: 1.32-4.59, p相似文献   

hTERT基因多态性与胃癌易感性的研究

人端粒酶逆转录酶(hTERT)作为端粒酶的关键酶参与了包括胃癌在内的多种肿瘤的发生和发展,有研究发现该基因的多个单核苷酸多态性(SNP)位点与多种恶性肿瘤具有不同程度的相关性。目的:探讨hTERT基因rs2853676和rs2853677位点SNP与胃癌遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测297例胃癌、105例萎缩性胃炎和402例对照组患者rs2853676和rs2853677位点的基因多态性,采用病理学检查和~(13)C-尿素呼气试验检测幽门螺杆菌(Hp)感染。结果:胃癌组rs2853676位点AA基因型频率显著高于对照组(15.2%对6.5%,P=0.01),AA基因型携带者患胃癌的风险增加2.47倍(95%CI:1.46~4.16)。三组rs2853677位点CC、TC、TT基因型频率差异无统计学意义。与对照组相比,萎缩性胃炎组和胃癌组Hp感染率显著升高(64.8%、56.9%对40.3%,P均0.01),OR值分别为2.73(95%CI:1.74~4.26)、1.96(95%CI:1.44~2.67)。Logistic回归分析发现,Hp感染与基因突变无明显交互作用。结论:hTERT基因rs2853676基因多态性与胃癌遗传易感性有关,其增加胃癌的风险与Hp感染可能无关。     

Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer

BACKGROUND & AIMS: Overexpression of cyclooxygenase-2 (COX-2) is implicated in many steps of cancer development. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to identify functional SNPs in the COX-2 promoter and evaluated their effects on the risk of developing esophageal squamous cell carcinoma (ESCC). METHODS: Thirty individual DNA samples were sequenced to search for SNPs, and the function of the SNPs was examined by a set of biochemical assays. Genotypes and haplotypes were analyzed in 1026 patients and 1270 controls, and odds ratios and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Three SNPs, -1290A-->G, -1195G-->A, and -765G-->C, were identified; the frequencies of variant alleles were 0.04, 0.51, and 0.02, respectively. The -1195G-->A change creates a c-MYB binding site and displays a higher promoter activity. The -1195A-containing haplotypes had significantly increased luciferase expression and COX-2 messenger RNA levels in esophageal tissues compared with the -1195G-containing counterparts. A case-control analysis showed a 1.72-fold (95% CI, 1.35-2.20) and 2.24-fold (95% CI, 1.59-3.16) excess risk of developing ESCC for the -1195AA or -765CC genotype carriers compared with noncarriers. A greater risk of developing ESCC was observed for A(-1195)-C(-765)-containing haplotypes compared with G(-1195)-G(-765)-containing haplotypes, suggesting an interaction between the -1195G-->A and -765G-->C polymorphisms in the context of haplotype. CONCLUSIONS: These findings indicate that genetic variants in COX-2 may play a role in mediating susceptibility to esophageal cancer.