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Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

World Journal of Gastroenterology 2001年第6期7卷 792-795页

作者： Lin Cai~1 Shun-Zhang Yu~2 Zuo-Feng Zhang~3 1 Department of Epidemiology,Fujian Medical University,Fuzhou 350004,Fujian Province,China2 Department of Epidemiology,Shanghai Medical University,Shanghai 200032,China3 Department of Epidemiology,UCLA School of Public Health,Los Angeles California,USA Department of Epidemiology Fujian Medical University Fuzhou 350004 Fujian Province China. zjcailin@***

AIM: genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized ***-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Poly

关键词： polymorphism, genetic Aged Asian Continental Ancestry Group Case-Control Studies China Cytochrome P-450 CYP2E1 Female Gene Frequency genetic Predisposition to Disease Humans Male Middle Aged Research Support, Non-U.S. Gov't Stomach Neoplasms

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GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

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World Journal of Gastroenterology 2004年第9期10卷 1240-1245页

作者： Jucimara Colombo Ana Elizabete Silva Andréa Regina Baptista Rossit Alaor Caetano Aldenis Albaneze Borim Durval Wohnrath Departamento de Biologia UNESP-Campus de So José do Rio Preto-SPBrazil Departamento de Doencas Dermatológicas Infecciosas e ParasitáriasFaculdade de MedicinaFAMERPSo José do Rio PretoSPBrazil Hospital de Base Faculdade de MedicinaFAMERE So José do Rio PretoSPBrazil Fundaco Pio Ⅻ BarretosBrazil

AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex ***2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three ***,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG *** GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.

关键词： polymorphism, genetic Adolescent Adult Aged Aged, 80 and over Brazil Case-Control Studies Chronic Disease Cytochrome P-450 CYP2E1 Female Gastritis Genotype Glutathione Transferase Humans Male Middle Aged Research Support, Non-U.S. Gov't Risk Factors Stomach Neoplasms

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genetic polymorphisms of CYP2D6 in Chinese mainland

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Chinese Medical Journal 2002年第12期115卷 1780-1784,145页

作者：纪玲潘世秀吴健民 Jacqueline Marti-Jaun Martin Hersberger 华中科技大学同济医学院附属协和医院检验科武汉430022 InstituteofClinicalChemistry

OBJECTIVE: To observe the significant differences in the frequencies of the cytochrome P450 2D6 (CYP2D6) alleles in Chinese popoulations. METHODS: Tetra-primer polymerase chain reaction (PCR), allele specific amplification (ASA) PCR and multiplex long PCR were developed to detect the CYP2D6 alleles * 2, * 3, * 4, * 5, * 6, * 8, * 10 and * 14 in 223 subjects from Chinese mainland. RESULTS: The CYP2D6 * 5 allele was the most frequent poor metabolizer (PM) allele in Chinese (7.2%), followed by CYP2D6 * 14 (2.0%) which was only detected in orientals. There was only 0.2% CYP2D6 * 4, and no CYP2D6 * 3, * 6 and * 8 were detected. In contrast to the Caucasians, the most frequent allele in Chinese was the * 10 allele with a frequency of 51.6%. CONCLUSION: The frequencies of PM alleles, CYP2D6 * 5 and CYP2D6 * 14, were higher; but the frequency of CYP2D6 * 10 was lower in mainland Chinese population than that in other orientals.

关键词： polymorphism, genetic Alleles China Cytochrome P-450 CYP2D6 Humans

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Genotype of ethanol metabolizing enzyme genes by oligonucleotide microarray in alcoholic liver disease in Chinese people

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Chinese Medical Journal 2002年第7期115卷 1085-1087,156+155页

作者：虞朝辉厉有名陈卫星乐敏浙江大学医学院第一附属医院杭州310003

OBJECTIVE: To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD). METHODS: Sixty-five healthy male controls and 165 alcoholisms (including 122 ALD patients and 43 male alcohol abusers without liver complications defined as alcohol-dependent) were analyzed by polymerase chain reaction and hybridized with oligonucleotide microarray to detect the polymorphisms of the ethanol metabolizing enzymes genes. RESULTS: The frequencies of alcohol dehydrogenase gene 2 * 1 ( ADH2 * 1 ) allele were shown as 37.69%, 46.51% and 59.02% in control, alcohol-dependent and ALD groups respectively; while those of ADH2 * 2 allele were shown as 62.31 %, 53.49% and 40.98% respectively. No ADH2 * 3 was detected in any of the subjects. The frequency of ADH2 * 1 was significantly higher in alcoholisms (ALD group and alcohol-dependent group) than in healthy controls ( P

关键词： Oligonucleotide Array Sequence Analysis Alcohol Dehydrogenase Aldehyde Oxidoreductases Genotype Humans Isoenzymes Liver Diseases, Alcoholic Male polymorphism, genetic

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Glutathione S-transferases M1,T1 genotypes and the risk of gastric cancer:A case-control study

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World Journal of Gastroenterology 2001年第4期7卷 506-509页

作者： Lin Cai Shun-Zhang Yu Zuo-Feng Zhang Department of Epidemiology.Fujian Medical University,Fuzhou 350004,Fujian Province,ChinaDepartment of Epidemiology,Shanghai Medical University,Shanghai 200032,China Department of Epidemiology,UCLA School of Public Health,Los Angeles California,USA Department of Epidemiology Fujian Medical University Fuzhou 350004 Fujian Province China. zjcailin@***

AIM: Glutathione S-transferases (GSTs) are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione S-transferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTT1 and GSTT1 and gastric cancer. METHODS: A population based case-control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTT1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS: An increase in risk for gastric cancer was found among carriers of GSTT1 null genotype. The adjusted odds ratio (OR) was 2.63 95% Confidence Interval (95% CI) 1.17-5.88, after controlling for age, gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTT1 null and GSTT1 non-null genotype was significantly higher than in those with both GSTT1 and GSTT1 non-null genotype (OR = 2.77, 95% CI 1.15-6.77). Compared with those subjects who never smoked and had normal GSTT1 genotype, ORs were 1.60 (95% CI:0.62-4.19) for never smokers with GSTT1 null type, 2.33 (95% CI 0.88-6.28) for smokers with normal GSTT1, and 8.06 (95% CI 2.83-23.67) for smokers with GSTT1 null type. CONCLUSIONS: GSTT1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinoge

关键词： Adult Aged Case-Control Studies Female genetic Predisposition to Disease Genotype Glutathione Transferase Humans Male Middle Aged polymorphism, genetic Research Support, Non-U.S. Gov't Risk Factors Smoking Stomach Neoplasms

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hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer

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World Journal of Gastroenterology 2003年第5期9卷 956-960页

作者： Jae-Il Kim Young-Jin Park Ki-Hong Kim Ji-Il Kim Byung-Joo Song Meung-Soo Lee Chul-Num Kim Seok-Hyo Chang Department of Surgery Ilsan Paik HospitalInje University College of Medicine.2240Daehwa-dongIlsan-guKoyang shiKyunggido 412-270Korea

AIM:To determine the association of hOGG1 (8-oxoguanine glycosylase I,OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors. METHODS:A case-control study with 125 colon cancer cases and 247 controls was conducted, RESULTS:There was no major difference in Ser326Cys genotype distribution between cases and *** meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95 % confidence interval;CI=1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR=4.31,95 % CI=1.64-11.48),but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/ Cys *** OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR=2.75,95 % CI=1.07-7.53) but not in Ser/Ser or Ser/ Cys carriers. CONCLUSION:These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall,but the Cys/ Cys genotype may alter the impact of some environmental factors on colon cancer development.

关键词： Base Sequence Case-Control Studies Colonic Neoplasms DNA DNA-Formamidopyrimidine Glycosylase Diet Female Genotype Humans Male Meat Middle Aged N-Glycosyl Hydrolases Odds Ratio polymorphism, genetic Risk Factors Smoking

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CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese

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Chinese Medical Journal 2002年第8期115卷 1248-1250,157-158页

作者：马芸汤旭磊常薇高林李茂欣严文伟兰州医学院附属一院内分泌科兰州730000 四川大学第一大学医院普通外科成都610041

OBJECTIVE: To investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han Chinese. METHODS: An A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A highly significant increase in the frequency of the G allele was seen in patients with type 1 diabetes compared with controls (66.1 % vs. 34.7%, respectively; P

关键词： Immunoconjugates polymorphism, genetic Antigens, Differentiation China Diabetes Mellitus Humans

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Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease

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Chinese Medical Journal 2002年第5期115卷 677-680,147-148页

作者：苏智广张思仲候一平张立廖林川肖翠英 Department of Medical genetics West China HospitalWest China Medical CenterSichuan UniversityChengdu 610041China Institute of Forensic Medicine West China Medical CenterSichuan UniversityChengdu 610041China Department of Cardiology West China HospitalWest China Medical CenterSichuan UniversityChengdu 610041China

OBJECTIVE: To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD. METHODS: Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. RESULTS: A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

关键词： Alleles Apolipoproteins Chromatography, High Pressure Liquid Coronary Disease DNA DNA Mutational Analysis Gene Frequency Humans Hypertriglyceridemia Lipoprotein Lipase Lipoproteins Lipoproteins, HDL Cholesterol polymorphism, genetic Research Support, Non-U.S. Gov't

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Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease

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Chinese Medical Journal 2004年第9期117卷 1288-1292页

作者：郑克勤张思仲贺勇张立张克兰黄德嘉孙岩 Department of Medical genetics West China Hospital Key Laboratory for Forensic Genomics and Forensic Medicine of Sichuan Province Division of Human Forensic Genomics Key Laboratory for Biotherapy of Human Diseases of the Ministry of EducationSichuan UniversityChengdu 610041China Department of Cardiology West China Hospital Sichuan UniversityChengdu 610041 China

BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.

关键词： polymorphism, genetic Adult Aged Carrier Proteins Coronary Disease Female Gene Frequency Glycoproteins Humans Lipids Lipoproteins, HDL Cholesterol Lipoproteins, LDL Cholesterol Male Middle Aged Research Support, Non-U.S. Gov't

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GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

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World Journal of Gastroenterology 2004年第23期10卷 3389-3393页

作者： Ahmed Abbas Karine Delvinquière Mathilde Lechevrel Pierre Lebailly Pascal Gauduchon Guy Launoy Fran ois Sichel GRECAN-EA1772 UFR des Sciences Pharmaceutiques Université de Caen Basse-Normandie et Centre Francois BaclesseAvenue du Général Harris14076 Caen cedex 05France GRECAN-EA1772 Université de Caen Basse-Normandie et Registre des Tumeurs Digestives du Calvados UFR de MédecineAvenue de la C te de Nacre14032 Caen cedexFrance

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(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,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological *** frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco *** ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(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.

关键词： Acyltransferases Adenocarcinoma Adult Aged Aged, 80 and over Carcinoma, Squamous Cell Case-Control Studies Cytochrome P-450 CYP1A1 Esophageal Neoplasms Female France genetic Predisposition to Disease Genotype Glutathione Transferase Humans Male Middle Aged polymorphism, genetic Research Support, Non-U.S. Gov't Risk Factors

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