代谢酶基因GSTM1和广西人群胃癌遗传易感性的关系

目的探讨代谢酶基因GSTM1多态性与广西地区人群胃癌遗传易感性之间的相关性。方法采用PCR技术检测广西地区121例胃癌患者和138例健康人的GSTM1基因多态性的分布频率,分析其与广西地区胃癌遗传易感性之间的相关性以及与吸烟、饮酒在胃癌易感性中的交互作用。结果胃癌组GSTM1（-）基因型频率（54．5％）显著高于对照组（39．1％）（X^2=6．140,P=0．013）。携带GSTM1（-）基因型的个体患胃癌的风险是携带GSTM1（＋）基因型个体的2．13倍（95％CI=1．079-1．831,P=0．013）。在吸烟者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险明显增加（OR=3．247,95％CI=1．067—2．328,P=0．015）。其增加程度远远高于总的胃癌风险（OR=2．129）。在饮酒者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险亦明显增加（OR=3．117,95％CI=1．020—2．863,P=0．033）。其增加程度远远高于总的胃癌风险（OR=2．129）。结论GSTM1（-）基因型显著增加广西地区人群患胃癌的风险,且显著增加吸烟、饮酒者患胃癌的风险。     

基因多态性与胃癌遗传易感性的关系

胃癌的发生是一个多因素、多步骤的复杂过程,环境因素与遗传因素的相互作用决定了这一过程的发展和结局.幽门螺杆菌（Hp）感染及饮食因素是经大量研究确认的胃癌高危因素.胃癌的遗传易感性分为强遗传易感性和弱遗传易感性.     

Ⅰ、Ⅱ相代谢酶基因多态性与肺癌遗传易感性研究进展

代谢酶基因多态性在人类恶性肿瘤发病中的作用已为越来越多的研究所证实,近几年,国内外开展了许多有关基因多态性和肺癌易感性的研究,本文就近年来对Ⅰ、Ⅱ相代谢酶基因多态性和肺癌遗传易感性关系的研究作一简要综述。     

毒物代谢酶基因多态性与结肠腺癌易感性关联

目的　探讨谷胱甘肽S 转移酶 (GST)M 1、T1和N 乙酰化转移酶 1(NAT1)基因多态与散发性结肠腺癌 (SCRAC)遗传易感性的关联。方法　应用PCR 限制性片段长度多态性 (RFLP)及多重PCR技术检测GSTM 1、GSTT1和NAT1基因多态性。结果　GSTM1、GSTT1空白基因型在对照组与病例组之间的频率比较 ,差异均无显著性 ,而NAT1 10的频率差异有显著性 (2 7.8%∶4 2 .3% ,P <0 .0 5 )。不同临床特征、老年或非老年SCRAC与对照组GSTM 1空白基因型的频率比较 ,差异均无显著性 ;GSTT1空白基因型在SCRAC远端 (6 6 .2 % ,P <0 .0 5 )、DukesC期 (80 .8% ,P <0 .0 1)及低分化(77.1% ,P <0 .0 1)中的频率均显著高于对照组 (4 7.5 % )。NAT1 10在不同部位SCRAC与对照组之间的频率差异无显著性 ,SCRAC在老年 (5 2 .7% ,P <0 .0 1)、DukesC期 (5 3.8% ,P <0 .0 5 )及中分化(5 4 .2 % ,P <0 .0 1)中的频率均显著高于对照组。结论　GSTT1空白基因型与远端SCRAC易感性有关 ,癌肿多处于DukesC期 ,多呈低分化腺癌 ;NAT1 10与SCRAC的遗传易感性有关 ,癌肿多见于老年患者 ,多处于DukesC期 ,多呈中度分化腺癌。     

CYP1A1、GSTM1基因多态性与肺癌遗传易感性的关系

目的 探讨CYP1A1 m1、m2位点和GSTM1基因多态性与肺癌遗传易感性的关系.方法采用病例对照研究方法和寡核苷酸芯片技术对110例山东汉族肺癌患者和125例正常对照者的基因组DNA进行CYP1A1、GSTM1基因多态性分析.结果 CYP1A1 m2位点、GSTM1基因型分布在肺癌组和对照组间存在统计学差异(P<0.05);携带CYP1A1 Val/Val基因型或GSTM1缺失基因型者患肺癌的危险性增高,其中吸烟个体患肺癌的风险进一步增加.结论 CYP1A1 m2位点和GSTM1基因多态性可能与肺癌发生有关,吸烟与CYP1A1、GSTM1基因具有协同作用.     

HLA-DQB1基因多态性与重症肌无力遗传易感性的关系

2001～2003年，我们运用PCR-SSP方法对中国北方地区49例重症肌无力(MG)与HLA-DQB1的相关性进行分析，以期进一步探讨MG免疫学异常的机制，并为寻找MG的易感基因提供线索。     

髓过氧化物酶基因多态性与原发性高血压遗传易感性的研究

目的:研究髓过氧化物酶(MPO)基因多态性与原发性高血压(EH)之间的遗传易感性.方法:采用分子流行病学方法,应用聚和酶链反应检测法107例EH和97例健康对照MPO基因型,比较不同基因型之间的分布频率及95%可信区间(CI),分析MPO基因多态性与EH易感性的关系.结果:正常人群GG、GA、AA基因型频率分别为56 7%、40 2%和3 1%,EH组分别为70 1%、29 0%和0 9%.携带GG者患EH的风险是基因型为至少一个等位基因A者的1 79倍 (95%CI 1 005~3 186).结论:本研究人群MPO基因多态与EH遗传易感性相关,等位基因A对EH易感性有保护作用.     

CYP2D6基因B突变与肌萎缩侧索硬化遗传易感性的关系

肌萎缩佃愫硬化(ALS)是一种选择性侵犯上、下运动神经元的中枢神经系统变性病。15％～20％的家族性AKS厦2％～7％的散发性ALS患者可检测到铜／锌超氧化物歧化酶(SODI)基因突变。我们对汉族人细胞色素P450206(CYP2D6)基因B突变与散发性ALS发病的关系进行了初步研究肌萎缩侧索硬化     

Association between dietary heterocyclic amine levels,genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of colorectal cancer: A hospital-based case-control study in Japan

Objective. Although associations between dietary HCA intake and colorectal cancer risk have been investigated, results have been suggestive but inconsistent. The aim of this hospital-based case-control study was to examine the impact of heterocyclic amine (HCA) intake on colorectal cancer risk. A further objective was to investigate the possible effect of genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on colorectal cancer. Material and methods. HCA exposure data were assessed using a self-administered food frequency questionnaire, and estimated HCA intake was verified by measuring the PhIP value in human hair. A total of 117 cases and 238 controls were included in these analyses. Odds ratios (ORs) were calculated using conditional logistic regression analysis to compare intake levels between the first and third tertiles. Results. No statistically significant increase in the risk of colorectal cancer with respect to total HCA intake was shown by analysis (OR = 0.99, 95% CI = 0.21–4.81). Furthermore, no association with risk was seen for individual HCAs, including PhIP, MeIQ, and MeIQx. Although variant alleles of CYP1A2 were associated with colorectal cancer (OR = 0.27; 95% CI = 0.07–0.99), genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with colorectal cancer. Conclusions. In the present study in subjects with low HCA exposure and with a limited sample size, no association was found between HCA intake and colorectal cancer, or any evidence of influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2.     

Impact of interaction between CYP1A1 genetic polymorphisms and smoking on coronary artery disease in the Han of China

Aims: To investigate the association of CYP1A1 genotype and additional gene–smoking interaction with coronary artery disease (CAD) risk based on a Chinese case-control study. Methods: A total of 1862 participants (1134 men, 728 women) were selected, including 620 CAD patients and 1242 normal controls. Logistic regression was performed to investigate association of CYP1A1 genotype, gene–gene, and gene–smoking interaction with CAD. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best gene–gene and gene–smoking interaction combination, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess if each selected interaction was calculated. Results: The carriers of homozygous mutant of rs4886605 polymorphism and heterozygous of rs4646903 are associated with increased CAD risk than those with wild-type homozygotes; OR (95% CI) was 1.98 (1.53–2.61) and 1.58 (1.24–1.96), respectively. The carriers of homozygous mutant of rs1048943 polymorphism is associated with decreased CAD risk than those with wild-type homozygotes, OR (95% CI) = 0.75 (0.60–0.93). GMDR model indicated a potential gene–gene interaction between rs4886605 and rs4646903 and a potential gene–smoking interaction between rs4886605 and smoking. Participants with rs4886605-CT or TT and rs4646903-TC or CC genotype have the highest CAD risk, compared to participants with rs4886605-CC and rs4646903-TT genotype; OR (95% CI) was 2.72 (2.03–3.61). In addition, we also found that smokers with rs4886605-CT or TT genotype have the highest CAD risk, compared to nonsmokers with rs4886605-CC genotype; OR (95% CI) was 3.07 (2.23–3.96). Conclusions: rs4886605 and rs4646903 are associated with increased CAD risk, but rs1048943 is associated with decreased CAD risk; we also found gene–gene interaction between rs4886605 and rs4646903 and gene–environment interaction between rs4886605 and smoking.     

Interaction models of CYP1A1, GSTM1 polymorphisms and tobacco smoking in intestinal gastric cancer

AIM: To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Val variant and glutathione S-transferase (GST) M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS: A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblings-in-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS: The frequency of the CYP1A1 Val variant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 (95% confidence interval (95%CI): 1.2-3.1, P<0.01). It showed a significant type 2 form of interaction model when both CYP1A1 Val variant allele and former tobacco smoking existed (i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYP1A1 variant alone). The interaction index gamma was 2.8, and OR(eg) (95%CI) was 5.0 (1.9-13.4). GSTM1 null genotype and former tobacco smoking were significant in a type 4 interaction model (i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects). The interaction index gamma and OR(eg) (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively. CONCLUSION: Different interaction models of CYP1A1 Val variant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.     

Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast cancer

ObjectiveTo investigate the relationship between CYP1A1 genetic polymorphisms and the invasion and metastasis of breast cancer.MethodsThe CYP1A1 gene polymorphism (an T-C transversion at nucleotide position 3801) was detected by the polymerase chain reaction and restriction fragment length polymorphism in 80 cases with breast cancer and 60 samples of normal breast tissue. The difference in genotypic distribution frequency between the groups, the correlation between the genotypes and the factors related to prognosis were analyzed.ResultsThe incidence of homozygous and variant genotypes had no difference between the breast cancer group and controls group (P=0.746). The proportion of variant genotype increased as clinical stage (P=0.006) advanced, as well as with increased numbers of lymph node metastases (P=0.010).ConclusionsIn patients with breast cancer there is a correlation between the CYP1A1 CC allele and some factors indicating poor prognosis, including more lymph node metastases as well as a more advanced clinical stage.     

基质金属蛋白酶-2和-9在食管鳞状细胞癌中的过表达

目的 探讨人食管鳞癌组织中基质金属蛋白酶(MMP)-2、-9的表达及其临床意义.方法 采用免疫组织化学法,检测57例食管鳞癌及10例食管正常黏膜石蜡标本中MMP-2、-9蛋白的表达情况.结果 食管鳞癌组织中MMP-2及MMP-9阳性表达率(40.3%,61.4%)显著高于正常组织(0.0%,10.0%)(P＜0.05).食管鳞癌组织中MMP-2及MMP-9阳性表达与淋巴结转移和癌组织浸润深度有显著相关性(P＜0.05),而与患者的性别、年龄和组织分化程度无显著相关性(P＞0.05).结论 MMP-2和MMP-9在食管癌中显著高表达,与食管癌的转移及侵袭有关,其异常表达可能共同参与食管癌的发生、发展过程,检测MMP-2、-9可作为食管癌病理学特点的参考指标.     

Analysis of CYP2E1 polymorphism for the determination of genetic susceptibility to gastric cancer in Koreans

BACKGROUND: Interindividual genetic differences in susceptibility to chemical carcinogens are among the most important host factors in human cancer. The present study was undertaken to reveal the association between the polymorphism of CYP2E1 (CYP2E1/PstI and CYP2E1/DraI) with genetic susceptibility to gastric cancer development in Koreans. METHODS: In the present study, 120 gastric cancer patients and 145 controls with no history of tumors were analyzed. CYP2E1 was determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP), or PCR and direct gel electrophoresis. RESULTS: The overall genotype distribution of CYP2E1 was not significantly different from that of controls. However, the genotype distribution of the patient subgroups with a history of heavy cigarette smoking (>30 pack/year) in the CYP2E1/PstI and CYP2E1/DraI polymorphisms were significantly different from those of non-smoking patients (P = 0.0122 and P = 0.0029, respectively). The difference was also noticeable in the younger patient subgroup (aged 相似文献   

广西肝癌高、低发区CYP3A5基因多态性的对比

目的: 研究广西肝癌高发区和低发区人群中CYP3A5基因多态性, 以探讨CYP3A5基因多态性与肝癌易感性的关系.方法: 收集广西医科大学第一附属医院2005/12-2006/09经病理确诊的72例肝细胞癌(HCC)患者的肝癌组织及其癌旁组织, 患者分别来自于肝癌高发区(黄曲霉素高污染区)和低发区. 12例血管瘤的瘤旁肝组织作为正常对照. 用PCR-RFLP法检测CYP3A5在上述标本中的多态性.结果: 广西肝癌高发区患者C Y P 3A5 * 1等位基因频率和基因型比(C Y P 3A5 * 1 /*1+CYP3A5*1/*3)与广西肝癌低发区患者比较, 差异有统计学意义( P<0.05);肝癌高发区人群与正常对照组比较, 差异有统计学意义( P<0.05);低发区与正常对照组之间比较, 差异无统计学意义.结论: C Y P 3A5 可能参与黄曲霉毒素B1(AFB1)相关性HCC的发生.     

CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.     

Cytochrome P450 (CYP) 1A2, sulfotransferase (SULT) 1A1, and N-acetyltransferase (NAT) 2 polymorphisms and susceptibility to urothelial cancer

Purpose Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP)1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetyltransferases (NAT) or sulfotransferases (SULT). Recently, several polymorphisms of CYP1A2, SULT1A1, and NAT2 that affect their activities have been reported.Methods In this study, 306 Japanese patients with urothelial transitional cell carcinoma and 306 healthy controls were compared for frequencies of CYP1A2, SULT1A1, and NAT2 genotypes.Results The frequencies of NAT2 intermediate or slow acetylator genotype were significantly higher in the urothelial cancer patients than in the healthy control subjects [odds ratio (OR)=1.49, 95% confidence interval (95% CI) 1.06–2.09, OR=3.23, 95% CI 1.72–6.08, respectively]. Stratifying by amount of smoking, among subjects who consumed >33.5 pack-years and carried the SULT1A1 *1/*1 or NAT2 slow acetylator genotype, the OR was 1.73 (95% CI 1.01–2.97) whereas it was 7.31 (95% CI 1.90–28.05) in non-smokers who carried the homozygous wild genotype, respectively. The relationships between CYP1A2, SULT1A1, and NAT2 polymorphisms and clinical findings including tumor differentiation, stage, and recurrence rate were analyzed. Only associations between NAT2 genotype and pathological findings were admitted, and the higher OR of NAT2 intermediate and slow acetylator genotype was more likely to present to a low-grade tumor (G1) among heavy-smokers.Conclusions Our results suggest that SULT1A1 *1/*1 and NAT2 slow acetylator genotypes might modulate the effect of carcinogenic arylamines contained in tobacco smoke, and that the modulation of NAT2 intermediate and slow acetylator genotype has a tendency to present a higher risk for highly differentiated tumors among heavy-smokers.