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.     

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.     

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.     

Cyclooxygenase-2 polymorphisms and the risk of esophageal adeno- or squamous cell carcinoma

AIM： TO determine whether -1195 A→G and/or -765 G→C polymorphisms in Cyclooxygenase-2 CCOX-2） may have a risk modifying effect on the development of esophageal carcinoma in a Dutch Caucasian population. METHODS： Two study groups were recruited, 252 patients with esophageal carcinoma and 240 healthy controls, matched for race, age, gender and recruiting area. DNA was isolated from whole blood and used for genotyping. PCR products were digested with restriction enzymes and products were analyzed by agarose gel electrophoresis. Odds ratios （OR） and 95% confidence intervals （CI） were estimated. RESULTS： The distribution of the -1195A→G polymorphism was significantly different in esophageal cancer patients compared to controls. The -1195 GG genotype resulted in a higher risk of developing esophageal adenocarcinoma （OR = 3.85, 95% CI： 1.45-10.3） compared with the -1195AA genotype as a reference. The -765 G→C genotype distribution was not different between the two groups. The GG/ GG haplotype was present more often in esophageal adenocarcinoma patients than in controls （OR = 3.45, 95% CI： 1.24-9.58; with AG/AG as a reference）. The same trends were observed in patients with squamous cell carcinomas, however, the results did not reach statistical significance. CONCLUSION： Presence of the COX-2 -1195 GG genotype and of the GG/GG haplotype may result in a higher risk of developing esophageal carcinoma.     

环氧化酶-2基因启动子区多态性与结直肠癌的易感性

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)基因启动子区的-1195(G/A,rs689466)及3’非翻译区的8473(T/C,rs5275)2个位点的基因多态性与结直肠癌(colorectal cancer,CRC)发病风险的相关性.方法:采用病例-对照研究,利用聚合酶链式反应和限制性片段长度多态性(polymerase chain reaction-restrictive fragment length polymorphism,PCR-RFLP)分析方法,对343例CRC患者和340例健康人的COX-2基因的2个位点的多态性进行检测,采用SPSS11.0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:COX-2-8473位点多态性的各基因型频率在病例组及对照组中分布均无显著差异(P>0.05),但COX-2-1195位点多态性的基因型频率在二组中分布有显著性差异(P<0.001),结果显示CRC患者COX-2-1195AG基因型在病例组的频率较对照组显著增高(校正后OR=2.23;95%CI:1.50-3.32),AA基因型在病例组中的频率亦较对照组高(校正后OR=2.46;95%CI:1.51-4.02),A等位基因携带者在病例组中的频率高于对照组(校正后OR=2.27;95%CI:1.55-3.34).各基因型分布在结肠癌及直肠癌中的分布无显著性差异(P>0.05).COX-2-1195A等位基因与淋巴结转移及TNM分期有显著相关性.结论:COX-2-1195位点AG/AA基因型是CRC的风险因素,且与CRC的淋巴结转移及TNM分期相关.     

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.     

COX-2 CA-haplotype is a risk factor for the development of esophageal adenocarcinoma

BACKGROUND: Neoplastic progression of BE towards EAC is associated with increased expression of COX-2. Increased COX-2 expression and enzyme activity is linked to the COX-2 CA haplotype, which consists of two gene polymorphisms in the COX-2 promoter. AIM: To study the impact of COX-2 haplotypes on the risk of developing EAC in patients with different forms of gastroesophageal reflux disease including BE. METHODS: DNA was obtained from a total of 635 Dutch white patients comprised of 140 patients with EAC, 255 with BE, and 240 with reflux esophagitis. COX-2 haplotypes were based on the gene polymorphisms at -765C/G and -1195A/G, as determined by PCR-RFLP. RESULTS: The tested population contained 170 (14%) CA- (-765C and -1195A) haplotypes, 829 (65%) GA and 271 (21%) GG-haplotypes, and no GC-haplotypes. The haplotype distribution in patients with reflux esophagitis and BE was similar (CA 12%, GA 68%, GG 21%), but differed significantly from that in patients with EAC (CA 21%, GA 58%, GG 20%). Particularly, the CA-haplotype was more common (P < 0.001) in EAC patients. CA-carriership was associated with EAC (OR 2.8, 95% CI 1.3-6.2, P= 0.008), with homozygosity for the CA-allele being statistically most significantly associated (OR 6.1, 95% CI 1.6-24.2, P= 0.01). CONCLUSION: The COX-2 CA-haplotype is more frequently observed in patients with EAC than in patients with BE and reflux esophagitis. These data suggest a direct link between COX-2 activity and neoplastic progression in patients with BE and reflux esophagitis.     

Cyclooxygenase 2 polymorphism and colorectal cancer： -765G〉C variant modifies risk associated with smoking and body mass index

AIM： To explore whether cyclooxygenase 2 （COX-2） -765G〉C polymorphism is associated with susceptibility of colorectal cancer （CRC） and to evaluate the risk of colorectal cancer in relation to environmental exposures and polymorphism. METHODS： We conducted a case-control study of 137 patients with colorectal cancer and 199 cancerfree controls in northeast China. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio （OR） and 95% confidence interval （95% CI）. RESULTS： The -765G〉C polymorphism was not independently associated with CRC risk. However, risk associated with the polymorphism differed by smoking and body mass index （BMI）. Smoking and BMI associated risks were stronger among those with -765GG genotype, showing that smokers had a 2.682-fold greater risk of CRC than nonsmokers （51/43 vs 68/126, P = 0.006）. Compared to those with a normal body mass index （BMI 18.5-22.9）, those with overweight （BMI 23-24.9） had a 3.909-fold higher risk of CRC （OR = 3.909, 95% CI = 2.081-7.344; P 〈 0.001）, while those with obesity （BMI 〉 25） had a 2.031- fold higher risk of CRC （OR = 1.107, 95% CI = 1.107-3.726; P = 0.022）. is not associated with an increased risk of CRC, -765GG genotype appears to be related to an increased risk in the presence of smoking and higher BMI.     

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。     

The COX-2 G/C -765 polymorphism may modulate the occurrence of cerebrovascular ischemia.

In the atherosclerotic plaque, cyclooxygenase-2 (COX-2) catalyzes prostaglandin E formation, which acts as a pro-atherogenic factor. A polymorphism, G/C -765, within the COX-2 promoter region modulates gene expression and the risk of cerebrovascular disease. We have evaluated the relation between COX-2 G/C -765 genotypes and the occurrence of cerebrovascular ischemia. We evaluated the COX-2 G/C -765 polymorphism in 110 consecutive patients with a documented history of acute ischemic cerebrovascular disease, in 110 age-matched and sex-matched subjects without such history, and in a general population (n = 324) from the same ethnical background. The frequency of the COX-2 -765C allele in patients [0.21; 95% confidence interval (CI), 0.16-0.26] was similar to those found in controls (0.28; 95% CI, 0.22-0.34) and in the general population (0.26; 95% CI, 0.23-0.29). Carriers of the CC genotype differed between patients (0.02; 95% CI, 0.00-0.05) and controls [0.10 (95% CI, 0.04-0.16), P = 0.019; odds ratio, 0.17 (95% CI, 0.04-0.79)] or the general population [0.08 (95% CI, 0.05-0.11), P = 0.023; odds ratio, 0.22 (95% CI, 0.05-0.95)]. In a multiple logistic regression analysis adjusted for confounding variables, smoking status (P < 0.001), atrial fibrillation (P = 0.004) and COX-2 G/C-765 polymorphism (P = 0.016) independently contributed to cerebrovascular ischemia, with CC carriers exhibiting a lower risk (odds ratio, 0.07; 95% CI, 0.01-0.61). Our data show an association between the COX-2 G/C-765 gene polymorphism and cerebrovascular ischemia, suggesting that the COX-2 gene is a susceptibility locus for the risk of cerebrovascular ischemic disease.     

GSTM1, GSTT1, GSTP1 and CYPIA1 genetic polymorphisms and susceptibility to esophageal cancer in a French population： Different pattern of squamous cell carcinoma and adenocarcinoma

AIM: To evaluate the association between CYPIA1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinorna (ADC) in a high risk area of northwest of France.METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles, GSTM1 *2/*2 and GSl-l-l*2/*2 null genotypes). A total of 79 esophagealcancer cases and 130 controls were recruited. RESULTS: GSTM2*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell cardnomas at a level close to statistical significance (OR = 1.83, 95% CI0.88-3.83, P= 0.11; OR = 3.03, 95% CI 0.93-9.90, P= 0.07,respectively). For GSTP1 polymorphism, no difference wasfound between controls and cases, whatever their histological status. Lower frequency of GST/-1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR=13.31, 95% CI 1.66-106.92, P&lt;0.01).CONCLUSION: In SCC, our results are consistent with the strong association of this kind of turnout with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses:(1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTTI‘, (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC,possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.     

A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus

Genetic association studies on the gene encoding receptor for advanced glycation end products (RAGE) and diabetes mellitus have reported conflicting results. To evaluate the association of RAGE gene four widely-evaluated polymorphisms (T-429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was conducted. A random-effects model was applied irrespective of between-study heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser, and 2843/3302 (n=13) for G1704T. Overall results detected no significant association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk. There was a trend toward an increased risk for alleles 1704T relative to 1704G (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup analysis by ethnicity indicated that allele 1704T conferred a significantly increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes mellitus indicated that association was potentiated exclusively for G1704T with diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias was observed. Our results provide convincing evidence regarding the association of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially diabetic retinopathy. Notably, this effect was more pronounced in East Asians.     

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。     

树突状细胞免疫受体基因多态性与抗环瓜氨酸肽抗体阴性类风湿关节炎相关性研究

目的 在汉族人群中研究树突状细胞免疫受体(DICR)基因多态性与类风湿关节炎(RA)及其不同亚型的易感相关性.方法 采用病例-对照研究法,选取年龄及性别相匹配的RA患者523例和健康对照510名;采用Taqman探针法检测DCIR基因rs2377422和rs10840759位点单核苷酸多态性(SNP);检测RA患者抗环瓜氨酸肽(CCP)抗体水平,分析DCIR基因多态性与不同亚型RA相关性;采用实时荧光定量聚合酶链反应(PCR)方法,定量检测DCIR在RA患者(233例)及健康者(71名)中mRNA表达水平,并进一步分析不同DCIR基因型对DCIR表达水平的影响.统计学处理采用X检验和多因素Logistic回归检验,2组间比较采用曼-惠特尼U检验.结果 ①DCIR SNP rs2377422与汉族RA发病明显相关(等位基因:OR 1.26;95％CI 1.06～1.50,P=0.005;基因型CC与TT+TC:OR 1.34;95％CI1.18～2.06,P=0.004);②DCIR SNP rs2377422主要与抗CCP抗体阴性RA发病相关(等位基因:OR 1.46;95％CI1.10～1.93,P=0.0091;基因型CC与TT+TC:OR 1.58;95％CI1.01～2.47,P=0.043);③和健康对照相比,RA患者外周血中DCIR基因mRNA水平显著增高(0.47-0.10与0.17-0.03,U=6502,P=0.000 38),且携带DCIR rs2377422 CC基因型的RA患者,其DCIR表达水平进一步明显增高(CC与TT+TC:0.429±0.069与0.238±0.023,U=1861,P=0.002).结论 汉族人群中DCIR rs2377422多态性主要与抗CCP抗体阴性RA易感相关;RA患者DCIR基因表达水平明显增高;DCIR rs2377422多态性可明显影响DCIR基因的表达.     

N-乙酰化转移酶1基因分型及其与散发性大肠腺癌易感性

目的　分析N 乙酰化转移酶 1 (NAT1 )各等位基因型及其与散发性大肠腺癌 (SCRAC)易感性之间的关联。方法　应用聚合酶链反应 (PCR) 限制性片段长度多态性分析 (RFLP)及多重PCR技术 ,检测中国湖北地区汉族无血缘关系的健康人 1 0 1例、SCRAC患者 1 0 4例的NAT1基因多态性。结果　 (1 )NAT1等位基因 1 0 (NATI 1 0 )频率在SCRAC患者与健康人之间及老年SCRAC患者与健康人之间的差异均有显著性 (前者P <0 0 5 ,OR =1 91 ,95 %CI=1 1～ 3 4;后者P <0 0 1 ,OR =2 91 ,95 %CI =1 48～ 5 90 ) ;在近端或远端SCRAC与健康人之间的差异无显著性 (P >0 0 5) ;(2 )DukesⅡ期、Ⅲ和Ⅳ期分别与健康人相比 ,其NAT1 1 0的频率差异均有显著性 (前者P <0 0 5 ,OR =2 48,95 %CI=1 1 8～ 5 2 0 ;后者P <0 0 5 ,OR =3 0 4 ,95 %CI =1 2 8～ 7 2 0 )。结论　NAT1 1 0与SCRAC易感性有关 ,其患者肿瘤浸润、转移早 ,与癌灶部位无关 ;是否与老年SCRAC易感性有关尚不清楚     

Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

AIM: To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer.METHODS: We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylori (H. pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H. pylori infection. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, including sex and age as confounding factors.RESULTS: The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer (OR 0.50, 95% CI: 0.26-0.95, P = 0.04) while the rs7789045 TT genotype showed an increased risk (OR 2.14, 95% CI: 1.20-3.82, P = 0.01). An elevated susceptibility to gastric cancer was observed in the subjects with H. pylori infection and the NaOD1 rs7789045 TT genotype (OR 2.05, 95% CI: 1.07-3.94, P = 0.03) or the NOD2 rs7205423 GC genotype (OR 2.52, 95% CI: 1.05-6.04, P = 0.04). Haplotype analysis suggested that the distribution of AGT (rs2907749, rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different (P corrected: 0.04), and the diplotype AGT/AGT was associated with an elevated gastric cancer risk (OR 1.98, 95% CI: 1.04-3.79, P = 0.04). The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H. pylori-related diffuse-type gastric cancer (OR 3.00, 95% CI: 1.38-6.53, P = 0.01; OR 4.02, 95% CI: 1.61-10.05, P < 0.01, respectively).CONCLUSION: Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.     

Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis

AIM:To evaluate the clinical significance of-765G/C and-1195G/A cyclooxygenase-2 (COX-2) gene polymorphisms in patients with pancreatic cancer (PC).METHODS:The study included 201 patients:85 with PC and 116 healthy controls.-765G/C and-1195G/A COX-2 gene polymorphisms were studied in DNA isolated from blood samples.The associations of the analyzed genotypes and clinical data at diagnosis were evaluated.RESULTS:We found an increased frequency of the homozygous-1195AA COX-2 genotype in patients with PC (53.7%...