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.     

CYP1A1及GSTM1基因多态性对肺癌发病的影响

目的探讨代谢活化酶细胞色素P4501A1（CYP1A1）及谷胱甘肽硫转移酶M1（GSTM1）基因多态性和环境暴露与肺癌易感性的关系。方法用聚合酶链反应—限制性片段长度多态性技术测定158例肺癌患者和455例对照者的CYP1A1及GSTM1基因多态性。结果与对照组比较，肺癌组吸烟、粉尘接触频率明显升高，而摄入蔬菜水果及消毒水频率明显降低（P均〈0．01）；两组CYP1A1与GSTM1基因各类型分布无统计学差异；CYP1A1突变型基因及GSTM1缺陷型与吸烟有协同致肺癌作用。结论吸烟、接触粉尘均增加肺癌发生率，而摄入蔬菜水果及消毒水降低其危险性；吸烟可增加CYP1A1基因突变型或GSTM1基因缺陷型个体肺癌发生的危险性。     

细胞色素P4501A1、谷胱甘肽转硫酶基因多态性与儿童急性淋巴细胞白血病的相关性研究

目的探讨生物代谢酶细胞色素P4501A1、谷胱甘肽转硫酶M1、T1基因多态性与儿童急性淋巴细胞白血病(ALL)的相关性。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(PCR-RFLP)技术对89例儿童ALL患儿以及90名健康对照者的CYP1A1 Msp Ⅰ多态(T264C)、GSTMI和GSTT1等基因的多态分布进行分析。结果儿童ALL组的CYP1A1基因Msp Ⅰ多态纯合子突变型(C型)的频率与对照组差异有统计学意义(P0.05),携带纯合子突变型的儿童患ALL的危险度比杂合子突变型(B型)与野生型(A型)儿童的高(OR=1.997,95% CI:1.024～3.896)。GSTM1缺失型分布频率与对照组相比差异有统计学意义(P0.05,OR=2.709,95%CI:1.427～5.146),GSTT1缺失型分布频率与对照组相比差异无统计学意义(P0.05)。同时携带CYPlAl C型、GSTM1、GSTT1缺失型的联合基因型儿童患ALL的风险增加(OR=2.235,95% CI:1.111～4.497)。结论 CYP1A1基因Msp Ⅰ多态纯合子突变型(C型)、GSTM1缺失型与儿童ALL的易感性可能相关,GSTT1缺失型与儿童ALL易感性可能不相关;同时携带CYP1A1 C型与GSTM1、GSTT1缺失基因型可能是儿童ALL发病的易感因素之一。     

CYP2E1,GSTM1基因多态性与甘肃地区食管癌易感性

目的探讨细胞色素氧化酶P450,GSTM1的基因多态性与甘肃地区食管癌遗传易感性之间的以及基因—基因的交互作用。方法运用病例对照分子流行病学研究方法和聚合酶链反应方法对食管癌病例组和正常对照组基因DNA进行CYP2E1,GSTM1基因分型。结果CYP2E1基因pst1多态性的三种基因型在食管癌组和对照组的频率差异有统计学意义（χ2=12.59,P〈0.05）。携带C1/C1基因型个体发生食管癌的风险是携带其他基因型2.80倍（OR=2.80,95%C I=1.21-6.46）。食管癌组GSTM1（-）基因型频率显著高于对照组（χ2=10.292,P〈0.05）,携带GSTM1（-）的个体患食管癌的危险性显著高于GSTM1（＋）基因型的个体（OR=2.337,95%C I=1.39-3.93）。联合分析CYP2E1基因pst1多态性和GSTM1基因多态性,携带有C1/C1和GSTM1（-）基因型的个体患食管癌的风险高于携带GSTM1（＋）和C1/C2或C2/C2基因型的个体（OR=3.00,95%C I=1.7375-5.182）。结论CYP2E1,GSTM1基因多态性与食管癌易感性有关联,CYP2E1基因C1/C1基因型是食管癌的易感性基因,而GSTM1基因缺失使食管癌危险性增加,CYP2E1,GSTM1存在交互作用。     

CYP1A1基因多态性和吸烟对肺癌的易感性

目的采用PCR-RFLP技术测定CYP1A1的mspI和exon 7位点多态性,并观察两者及吸烟对肺癌易感性的影响。方法研究采用等位基因特异性扩增和PCR-RFLP技术,分析CYP1A1基因3'端限制性内切酶mspI和exon 7位点基因的基因多态性。结果 CYP1A1的mspI和exon 7位点各自基因型分布频率均无显著性差异(χ2=1.34,P>0.05);其中mspI突变型TC和CC患肺癌的相对危险性增加(OR=1.18,P<0.05;OR=1.49,P<0.05);exon 7突变型Ile/Val和Val/Val患肺癌的相对危险性亦增加(OR=1.35,P<0.05;OR=2.70,P<0.05);两多态位点联合作用分析,表明携带突变基因的个体肺癌易感性较高(OR=4.42,P<0.05)。对肺癌易感性与吸烟的关系分析,吸烟者患肺癌的危险性是不吸烟者1.77倍(χ2=5.72,P<0.05);携带突变基因且吸烟者肺癌易感性显著增加(OR=2.16,P<0.05;OR=2.63,P<0.05)。结论 CYP1A1突变型基因可能增加肺癌的易感性;CYP1A1突变型基因与吸烟之间存在协同作用,明显提高了患肺癌的风险性。     

GSTM1基因多态性与中国汉族人群肺癌易感性的Meta分析

目的 探索谷胱甘肽硫转移酶M1(GSTM1)基因多态性与中国汉族人群肺癌发生的相关性.方法 检索2011年8月之前GSTM1基因多态性与肺癌相关性的相关文献,根据纳入、排除标准选择符合要求的文献,整理GSTM1功能型基因型、缺失型基因型频数或频率,采用Mantel-Haenszel固定效应模型分析合并OR值,并用漏斗图和Egger线性回归分析评估文献的发表偏倚.结果 GSTM1(-)基因型携带者发生肺癌的风险是GSTM1(+)基因型携带者的1.64倍(95％CI:1.43～1.87),有统计学意义(Z=7.19,P＜0.01);发表偏倚的漏斗图对称,Egger线性回归分析回归截距为-0.422(95％CI:-3.011～2.167),无发表偏倚(P=0.734).结论 GSTM1基因是肺癌发生的易感基因,其中GSTM1缺失型基因型是中国汉族人群发生肺癌的风险因子.     

解毒酶基因谷胱甘肽硫转移酶M1多态性与黄曲霉毒素B1相关性肝细胞癌易患性研究

目的探讨解毒酶基因谷胱甘肽硫转移酶M1(GSTM 1)多态性与黄曲霉毒素B1(AFB1) 相关性肝细胞癌(HCC)风险的相关性。方法应用聚合酶链反应技术对广西地区AFB1高污染区140 例HCC患者和536例对照人群的GSTM1基因多态性进行检测,进行以医院为基础的病例对照研究。结果(1)GSTM1-present基因型为HCC保护基因型,而GSTM1-null基因型为HCC风险基因型,其校正风险值OR(95%可信区间CI)为2.07(1.20-3.5 7);(2)在AFB1暴露中低度与高度两个层次, GSTM1基因多态性均增加HCC危险性,其校正OR(95%CI)分别为1.92(0.92-4.00)和1.80(0.77- 4.17)。结论解毒酶基因GSTM1多态性与HCC易患性相关,其缺失型增加患HCC风险;GSTM1在中低度和高度AFB1暴露时均与HCC易患性相关,但在中低度暴露时更明显。     

GSTM1基因多态性与肺癌发病的相关性研究

目的探讨谷胱甘肽硫转移酶M1（GSTM1）基因多态性与肺癌易感性的关系，以期用于肺癌的筛检。方法用PCR法分析56例肺癌（简称肺癌组）和42例健康对照组GSTM1基因型，并用Logistic多因素回归法分析可能影响GSTM1的职业环境因素、生活习惯、及宿主个体因素。结果肺癌组GsTM1基因缺失型[GSTM1（-）]发生率达71．43％，显著高于对照组的45．24％，差异有统计学意义，P〈0．05；GSTM1（-）型与肺癌呈高度联系强度，OR=3．09（95％CI=1．32～6．94）；Logistic回归分析表明，职业接触PAHs（OR=6．6939，P=0．009）、吸烟（OR=9．7058，P=0．0010）、既往肺病史（OR=7．5233，P=0．0465）与GST M1（-）型相关。结论GST M1（-）型个体增加了肺癌发生的风险性，可作为宿主肺癌易感性的遗传标志。     

吸烟者细胞色素P4501A1基因多态性与冠心病的相关性分析

目的 探讨吸烟者细胞色素P4501A1（CYP1A1）基因MspI多态性与冠心病易感性的关系。方法 以病例-对照研究的方法,采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测349例冠心病组和404例对照组CYPlAl的基因多态性,并按吸烟指数[smoking index（SI）,吸烟支数／d×吸烟年数]的不同分析患冠心病的风险。结果 CYP1A1 MspI有3种基因型：野生型TT、突变杂合型TC和突变纯合型CC。冠心病组与对照组比较基因型分布差异无统计学意义（X^2=3．224,P=0．200）。在吸烟者中,冠心病组与对照组比较基因型分布差异有统计学意义（X^2=9．403,P=0．009）。冠心病组纯合型CC显著高于对照组,P：0．002,比值比（oddsration,OR）为3．142（95％可信区间1．481～6．668）。在低吸烟量组（I≤SI≤400）和高吸烟量组（SI〉400）中,杂合型TC和纯合型CC合计的OR值分别为2．215（95％可信区间1．087～4．510）及1．407（95％可信区间0．709～2．791）。结论 吸烟者CYP1A1基因MspI多态性与冠心病的发病可能相关。     

代谢酶基因CYP 1A1与广西胃癌遗传易感性的关系

目的探讨代谢酶基因CYP 1A1MSP1多态性与广西地区汉族、壮族人群胃癌遗传易感性之间相关性。方法采用PCR-RFLP技术检测广西地区汉族、壮族人群中121例胃癌患者和138例健康人CYP1A1MSP1多态性的分布频率,分析其与广西地区汉族、壮族人群胃癌遗传易感性的相关性及与吸烟、饮酒在胃癌易感性中的相互作用。结果 (1)CYP 1A1MSP1三种基因型(m1/m1、m1/m2、m2/m2)分布频率在两组间比较差异无统计学意义(χ2=0.901,P=0.342);(2)携带CYP1A1MSP1突变m2基因型的个体较携带m1/m1基因型的个体患胃癌的风险增加(OR=1.509),但差异无统计学意义(P=0.342)。结论单独的CYP 1A1基因MSP1多态性与广西地区汉族、壮族人群胃癌易感性无明显相关性。     

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

MIM: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 PCR.CYP2E1/PsА 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 groups.However,a significant difference between CG and C was observde,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjicts,and the GSTM1 null genotype was observed mainly in individuals with chronic gastritis infected with H pylori.CONCLUSION:Our findings indecate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.     

Phase Ⅰ/Ⅱ enzyme gene polymorphisms and esophageal cancer risk: A meta-analysis of the literature

AIM: Phase Ⅰ/Ⅱ enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations.METHODS: Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1MspI polymorphisms, CYP2E1 RsaI polymorphisms,GSTM1 null type, GSTT1 null type and GSTP1 Ile104Val.All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygousnon-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1. A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk,with ORs (95%CI) compared with Ile/Ile of 1.37 (1.09-1.71),2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters.CONCLUSION: A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.     

Phase Ⅰ／Ⅱ enzyme gene polymorphisms and esophageal cancer risk： A meta-analysis of the literature

AIM: Phase I/II enzymes metabolize environmental carcinogens and several functional polymorphisms have been reported in their encoding genes. Although their significance with regard to esophageal carcinogenicity has been examined epidemiologically, it remains controversial. The present systematic review of the literature was performed to clarify associations. METHODS: Eligible studies were case-control or cohort studies published until September 2004 that were written in any language. From PubMed and a manual review of reference lists in relevant review articles, we obtained 16 studies related to the CYP1A1 Ile-Val substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 Rsal polymorphisms, GSTM1 null type, GSTT1 null type and GSTP1 Ilel04Val. All were of case-control design. Summary statistics were odds ratios (ORs) comparing heterozygous-, homozygous-non-wild type or these two in combination with the homozygous wild type, or the null type with the non-null type for GSTM1 and GSTT1, A random effect model was used to estimate the summary ORs. A meta-regression analysis was applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile-Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs (95%CI) compared with lie/lie of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44 (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant association was found between esophageal cancer risk and the other genetic parameters. CONCLUSION: A significant association exists between the CYP1A1 Ile-Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the internal exposure to activated carcinogens may increase the risk of esophageal cancer.     

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.     

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

AIM: To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Va/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 siblingsin -law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS: The frequency of the CYP1A1 Va/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 y was 2.8, and OReg(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 y and OReg (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively. CONCLUSION: Different interaction models of CYP1A1 Va/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 genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh＇s esophageal squamous cell cancer in Xinjiang, China

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in China. METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls. RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) than in control subjects (24.0%) (P<0.05; OR, 11.13; 95%CI, 5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vs the control group (3.8%) (P<0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P<0.05; OR, 13.42; 95%CI, 6.29-28.3). CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased the susceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.     

Polymorphisms of drug-metabolizing enzymes and risk of childhood acute lymphoblastic leukemia

The involvement of phase I and II enzymes is well documented in the metabolism of a wide range of drugs and xenobiotics. Single-nucleotide polymorphisms (SNPs) of these enzymes are also known to alter their protein expression and function. Moreover, genetic susceptibility and environmental exposure have been proposed to be an etiology of cancer. We hypothesized that polymorphisms of these enzymes might affect the risk of childhood acute lymphoblastic leukemia (ALL). CYP 1A1, CYP 3A4*1B, CYP 3A5*3, CYP 3A5*6, GSTM1, and GSTT1 polymorphisms were genotyped by using PCR-RFLP in 107 children with ALL and 320 healthy controls. Allele and genotype frequencies of each of the SNPs were compared between two groups. It was found that the allele frequencies of CYP 1A1*1, *2A, *2B, and *4 were not different between cases and controls. CYP 3A4*1B allele frequency was only 0.8% and 0.9% in ALL and controls, respectively. CYP 3A5*1/*1, *1/*3, and *3/*3 genotype frequencies showed no statistically significant difference between patients and controls. CYP 3A5*6 was not detected in our population. The GSTM1 null genotype was significantly increased in children with ALL (OR 1.7; 95% CI, 1.0, 2.7). In contrast, the GSTT1 null genotype did not show this effect. Our data thus demonstrate that the GSTM1 null genotype might increase the risk of childhood ALL in a Thai population.     

Association of CYP1A1 and GSTM1 Polymorphisms With Oral Cancer Susceptibility: A Meta-Analysis

Our meta-analysis was aimed to evaluate the association of CYP1A1 and glutathione-S-transferase M1 (GSTM1) polymorphisms with oral cancer susceptibility.The related articles were searched in PubMed, Embase, and CNKI databases. Fifty eligible studies were included in our meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the relationship of CYP1A1 (rs4646903 and rs1048943) and GSTM1 polymorphisms with oral cancer risk. A random-effects model or fixed-effects model was employed depending on the heterogeneity.In overall analysis, CYP1A1 rs4646903 polymorphism was associated with the risk of oral cancer (CC vs TT: OR 1.65, 95% CI 1.33–2.05; CC vs TC+TT: OR 1.77, 95% CI 1.48–2.11; C vs T: OR 1.17, 95% CI 1.07–1.28), whereas rs1048943 showed no obvious association with oral cancer susceptibility. Moreover, subgroup analysis by ethnicity demonstrated that rs4646903 and rs1048943 both related with increased risk of oral cancer in Asians. Moreover, the analysis based on source of control suggested that rs4646903 could increase the risk for oral cancer in both population- and hospital-based populations, whereas no remarkable relationship of rs1048943 with oral cancer susceptibility was observed. For GSTM1 gene, null genotype appeared to be a risk factor for oral cancer (null vs present: OR 1.23, 95% CI 1.12–1.34), which was also proved in the subgroup analysis.The results demonstrated that CYP1A1 rs4646903 and null genotype of GSTM1 polymorphisms might serve as risk factors for oral cancer.     

基因多态性及常见危险因素与胃癌易患性的研究

目的探讨中国汉族人群细胞色素P450(CYP)1A1基因型、谷胱甘肽巯基转移酶(GST) M1基因型及常见危险因素与胃癌易患性的关系,为胃癌高危人群的确定和胃癌的一级预防提供分子生物学手段。方法所有研究对象经胃镜和病理检查分为胃癌(GC,仅包括胃腺癌)组102例、慢性萎缩性胃炎(CAG)组110例、慢性浅表性胃炎(CSG)组110例、胃溃疡(GU)组62例、十二指肠溃疡(DU)组62例及正常对照组62例。采用统一的调查表对每个研究对象进行调查,调查项目包括年龄、性别、学历、职业、吸炯史、饮酒史、饮食习惯、肿瘤家族史等。采用序列特异性引物的聚合酶链反应(PCR-SSP)方法检测CYP1A1基因型及GSTM1基因型测定组的基因型频率,ELISA法测定幽门螺杆菌(Hp)感染,病例对照研究方法进行流行病学分析。结果单因素分析显示与胃癌有关联的危险因素为年龄、性别、文化程度、职业、Hp感染、吸烟、CYP1A1 G/G基因型、GSTM1空白基因型,其中大蒜为保护性因素;多因素分析显示与胃癌有关联的危险因素分别为Hp感染、CYP1A1 G/G基因型、GSTM1空白基因型,大蒜仍为保护性因素。CYP1A1 G／G基因型及GSTM1空白基因型对胃癌的发生具有协同作用。Hp感染与CYP1A1 G／G基因型、GSTM1空白基因型对胃癌的发生存在协同作用;吸烟与CYP1A1 G/G基因型、GSTM1空白基因型存在协同作用。结论具有CYP1A1 G/G或GSTM1基因型的个体发生胃癌的危险性增加,而同时有两种基因型的个体发生胃癌的危险性更高,这两种基因型可以认为是胃癌易患性的标志。     

Kimchi and soybean pastes are risk factors of gastric cancer

AIM: This case-control study investigated the effects of kimchi,soybean paste, fresh vegetables,nonfermented alliums, nonfermented seafood, nonfermented soybean foods, and the genetic polymorphisms of some metabolic enzymes on the risk of gastric cancer in Koreans. METHODS: We studied 421 gastric cancer patients and 632 age- and sex-matched controls. Subjects completed a structured questionnaire regarding their food intake pattern. Polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase mu 1 (GSTM1),glutathione S-transferase theta 1 (65777) and aldehyde dehydrogenase 2 (ALDH2) were investigated. RESULTS: A decreased risk of gastric cancer was noted among people with high consumption of nonfermented alliums and nonfermented seafood. On the other hand, consumption of kimchi, and soybean pastes was associated with increased risk of gastric cancer. Individuals with the CYP1A1 Ile/Val or Val/Val genotype showed a significantly increased risk for gastric cancer. Increased intake of kimchi or soybean pastes was a significant risk factor for the CYP1A1 lie/lie, the CYP2E1 c1/c1,the GSTM1 non-null, the GSTT1 non-null, or the ALDH2 *1/*1 genotype.In addition, eating soybean pastes was associated with the increased risk of gastric cancer in individuals with the GSTM1 null type. Nonfermented alliums were significant in individuals with the CYP1A1 lie/lie, the CYP2E1 c1/c2 or c2/c2, the GSTT1 null, the GSTT1 non-null, or the ALDH2 *1/*2 or *2/*2 genotype,nonfermented seafood was those with the CYP1A1 lie/lie,the CYP2E1 c1/c1, the ALDH2 *1/*1 genotype or any type of GSTM1 or GSTT1. In homogeneity tests, the odds ratios of eating kimchi for gastric cancer according to the GSTM1 or 65777 genotype were not homogeneous. CONCLUSION: Kimchi, soybean pastes, and the CYP1A1 Ile/Val or Val/Val are risk factors,and nonfermented seafood and alliums are protective factors against gastric cancer in Koreans. Salt or some chemicals contained in kimchi and soybean pastes, which are increased by fermentation,would play important roles in the carcinogenesis of stomach cancer.Polymorphisms of the CYP1A1, CYP2E1, GSTM1, GSTT1, and ALDH2 genes could modify the effects of some environmental factors on the risk of gastric cancer.