修复基因多态性与晚期肺癌顺铂化疗近期疗效的研究

目的:探讨X射线损伤修复交叉互补基因1(XRCC1)与接受顺铂方案化疗的晚期非小细胞肺癌(NSCLC)患者疗效的关系。方法:经病理确诊的晚期非小细胞肺癌患者62例,接受含铂方案化疗至少2周期后评价疗效,采用TaqMan探针实时荧光定量聚合酶链反应(PCR)法和直接测序法对患者外周血XRCC1第399位密码子进行多态性分析,分析各基因型与晚期非小细胞肺癌患者近期疗效的相关性。结果:XRCC1399至少携带1个Gln等位基因携带者的疗效不如Arg等位基因携带者(14.81%vs.42.86%,OR=0.24,95%CI为0.049 2～0.908 7,P<0.05)。结论:XRCC1 399多态性与NSCLC患者对铂类药物化疗的敏感性相关。     

XPD751基因多态性与晚期非小细胞肺癌化疗敏感性及毒性的相关性探讨

目的探讨人类着色性干皮病D组基因(XPD)与接受含铂方案化疗的晚期非小细胞肺癌(NSCLC)患者的近期疗效及毒副反应的关系。方法经病理确诊的晚期非小细胞肺癌患者62例,接受含铂方案化疗至少2周期后评价疗效,采用TaqMan探针实时荧光定量聚合酶链反应(PCR)法和直接测序法对患者外周血XPD第751位密码子进行多态性分析,分析各基因型与晚期非小细胞肺癌患者近期疗效及毒副反应的的相关性。结果 XPD751基因多态性与NSCLC患者对铂类药物化疗的有效率无关(P>0.05,95%CI=0.2924~4.3594,OR=1.1290)。携带XPD751Lys/Gln基因型患者其消化道反应较携带Lys/Lys基因型患者明显(P<0.05)。而在血液学方面的差异无统计学意义(P>0.05)。结论 XPD751基因多态性与NSCLC患者对铂类药物化疗的敏感性无关,而对预测其毒副反应有一定价值。     

ERCC1、BRCA1基因蛋白在晚期NSCLC中的表达及其临床意义

目的探讨ERCC1和BRCA1基因蛋白在晚期非小细胞肺癌(NSCLC)中的表达及其与铂类化疗近期疗效之间的关系。方法采用免疫组化法对152例晚期非小细胞肺癌中ERCC1和BRCA1基因蛋白的表达进行检测,并通过Lgistic回归的方法对ERCC1、BRCC1基因蛋白表达与各临床特征(性别、年龄、是否吸烟、临床分期、病理类型)及晚期非小细胞肺癌含铂化疗方案的近期有效率进行分析。结果 ERCC1和BRCA1基因蛋白的表达与各临床特征之间均无相关性(P>0.05),ERCCl基因蛋白表达阴性者,应用含铂方案化疗,其近期疗效明显高于ERCCl基因蛋白表达阳性的非小细胞肺癌患者(P<0.05),BRCA1基因蛋白的表达与含铂化疗近期疗效无关(P>0.05)。结论 ERCC1基因蛋白可预测非小细胞肺癌对含铂联合化疗方案的敏感性。     

肺癌患者谷胱甘肽S-转移酶P1基因Ile105Val多态性分析

目的:分析肺癌患者谷胱甘肽S-转移酶P1(GSTP1)基因Ile105Val单核苷酸多态性.方法:采用病例-对照研究方法,以聚合酶链反应-限制性片段长度多态(PCR-RFLP)技术,检测121例正常对照和121例肺癌患者GSTP1基因Ile105Val多态性基因型分布,并比较各基因型与肺癌易感性的关系.结果:肺癌患者中,携带GSTP1突变等位基因的基因型Ile/Val Val/Val的频率为51.2%,高于对照组的33.1%(P=0.004);至少携带一个Val等位基因的个体发生肺癌风险是Ile/Ile基因型个体的2.13倍(95%CI1.27～3.58),且病理分型分析显示风险增加主要在鳞癌组.经吸烟分层后,仅增加吸烟者的风险.结论:GSTP1基因Ile105Val多态可能与中国人肺癌易感性有关,可用于对肺癌易感个体的预警和预防.     

晚期结直肠癌GSTP1基因多态性与奥沙利铂化疗效果关系

目的 探讨谷胱甘肽S转移酶P1(GSTP1)基因 Ile105Val(A→G)多态性与晚期结直肠癌对以奥沙利铂为主方案化疗效果的关系.方法 Ⅳ期结直肠癌病人102例,化疗前取静脉血应用TaqMan-MGB探针等位基因分型技术检测GSTP1基因Ile105Val的多态性.给予病人以奥沙利铂为主的方案化疗,2～3个周期后进行临床疗效评价并统计疾病进展时间(TTP),分析GSTP1基因型与化疗敏感性及生存期的关系.结果 102例晚期结直肠癌病人中,A/A基因型54例 (52.94%),G/G基因型10例(9.80%),G/A基因型38例(37.25%).G/G+G/A基因型病人的化疗有效率为62.5%, A/A基因型病人的化疗有效率为25.9%,两者之间差异有显著性(χ2=14.21,P<0.01;OR=4.741,95%CI=1.556～13.207).102例病人中位TTP为7.9 个月,G/G+G/A基因型为9.7 个月,A/A基因型为6.4 个月,两者比较差异有显著性(χ2=35.001,P<0.01).结论 GSTP1 Ile105Val基因多态性可能与晚期结直肠癌病人对奥沙利铂化疗的敏感性及生存时间相关.     

晚期胃癌XPG及GSTP1基因多态性与奥沙利铂化疗效果的关系

目的 探讨人着色性干皮病G组(XPG)及谷胱甘肽巯基转移酶P1(GSTP1)基因多态性与晚期胃癌以奥沙利铂为主的化疗敏感性的关系.方法 80例Ⅳ期胃癌病人化疗前采集外周静脉血,提取DNA,用实时荧光PCR技术检测XPG C46T及GSTP1 A105G基因的单核苷酸多态性(SNP)分型,比较不同基因型与化疗效果的关系.结果 80例病人XPG C46T基因C/C与T/T+C/T及GSTP1 A105G基因A/A与A/G+G/G基因型化疗有效率比较差异均有显著意义(X2=5.459、5.291,P＜0.05).同时携带XPG C46T C/C和GSTP1 A105G A/G+G/G基因型病人化疗敏感性是同时携带XPG C46T C/T+T/T和GSTP1 A105G A/A基因型病人的4.886倍(OR=4.886,P＜0.05).结论 XPG C46T、GSTP1 A105G基因多态性可能与晚期胃癌病人接受以奥沙利铂为主一线化疗药物化疗后的效果有关.     

TP方案治疗晚期非小细胞肺癌近期疗效观察

目的：观察紫杉醇加顺铂（TP方案）治疗晚期非小细胞肺癌的近期疗效和毒副作用。方法：晚期非小细胞肺癌患者用TP方案化疗,至少2个周期,评价疗效和毒副作用。结果：TP方案治疗晚期非小细胞肺癌的有效率为52％,毒副作用轻微,主要为消化道反应和骨髓抑制。病人可耐受。结论：紫杉醇加顺铂方案治疗晚期非小细胞肺癌疗效好。毒副作用小．     

吉西他滨联合顺铂化疗方案治疗晚期非小细胞肺癌的近期疗效观察

目的:评价吉西他滨联合顺铂化疗方案治疗晚期非小细胞肺癌的近期疗效和不良反应.方法:晚期非小细胞肺癌患者48例,给予GP联合方案化疗.结果:总有效率60.41%,主要不良反应为骨髓抑制和胃肠道反应.结论:吉西他滨联合顺铂化疗方案治疗晚期非小细胞肺癌有较好的疗效,不良反应轻,值得临床研究和推广.     

GC方案与GP方案治疗晚期非小细胞肺癌的疗效比较

目的对比分析GC方案（吉西他滨联合卡铂）与GP方案（吉西他滨联合顺铂）治疗晚期非小细胞肺癌的疗效,探究临床治疗晚期非小细胞肺癌的有效化疗方案。方法将102例晚期非小细胞肺癌患者随机分为GC组与GP组各51例,前者接受GC方案治疗,后者接受GP方案治疗,所有患者均接受至少2个周期的化疗,对比分析两组患者的疗效及安全性。结果①两组患者近期疗效相比差异无统计学意义（P〉0.05）。②两组患者1年生存率相比差异无统计学意义（P〉0.05）。③两组患者白细胞减少、血红蛋白减少、血小板减少、脱发的发生率相比差异无统计学意义（P〉0.05）,但是GC组恶心、呕吐发生率显著低于GP组,两组比较差异有统计学意义（P〈0.05）。结论 GC方案与GP方案治疗晚期非小细胞肺癌的疗效相近,但是GC方案消化道反应较轻,因此更适用于年老体弱的晚期非小细胞肺癌患者。     

晚期非小细胞肺癌ERCC1表达与含顺铂方案化疗疗效的相关性研究

目的研究并探讨晚期非小细胞肺癌切除修复交叉互补基因1(excisionrepair cross-complementing 1,ERCC1)表达与含顺铂方案化疗疗效的相关性。方法于2012年1月至2014年1月,选择我院收治的100例晚期非小细胞肺癌患者作为研究对象,采取计算机随机数字分组法分为对照组30例、观察组70例,对照组采用标准NP方案化疗,观察组先检测ERCC1表达,将观察组分为ERCC1高表达组和ERCC1低表达组,分别采用单药N方案、标准NP方案化疗,比较各组患者的近期疗效、毒副反应、3年生存率。结果观察组的近期总有效率高于对照组(P0.05),ERCC1高表达组和ERCC1低表达组比较无统计学差异(P0.05);各组的毒副反应发生率比较,差异无统计学意义(P0.05);观察组的3年生存率高于对照组(P0.05),而观察组两个亚组之间比较无统计学差异(P0.05)。结论晚期非小细胞肺癌患者的ERCC1表达与含顺铂化疗方案有关,ERCC1高表达患者易对顺铂耐药,临床上可将ERCC1表达作为晚期非小细胞肺癌个体化化疗方案制定的重要参考依据。     

人工修饰双等位基因特异性引物结合SYBR Green I荧光PCR法检测GSTP1基因多态性

目的 建立人工修饰双等位基因特异性引物结合SYBR Green I荧光PCR法检测GSTP1第105个密码子基因多态性的方法,并利用该法研究GSTP1 第105个密码子在广西百色市人群遗传特征,为进一步研究GSTP1基因多态性与疾病的发生易感性研究奠定基础.方法 采用人工修饰双等位基因特异性引物结合SYBR Green I荧光PCR法技术对211例广西百色市健康成人进行GSTP1 Ile105Val基因分型,并分析是否存在性别差异及与国内外其他人群分布频率差异.结果 人工修饰双等位基因特异性引物结合SYBR Green I荧光PCR法GSTP1基因型检测结果与PCR产物测序结果一致,用此法检测出广西百色市女性和男性人群GSTP1 Ile105Val均以A等位基因为主,分别为79.7%和84.5%;AA野生纯合子型、AG杂合子型和GG突变纯合型在女性人群中分别为62.2%、35.1%和2.7%,男性人群则为71.0%、27.0%和2.0%.经统计学分析,广西GSTP1Ile105Val等位基因和基因型分布频率无性别差异,与辽宁、回族、印度、俄罗斯族等人群相应位点基因型分布频率无差异,但与国内维族、朝鲜族、蒙古族、高加索女性相比差异有统计学意义(P<0.01).结论 人工修饰双等位基因特异性引物结合SYBR Green I荧光PCR法是一种快捷、准确的基因多态性检测方法.广西人群GSTP1基因 Ile105Val呈多态性分布,基因型分布频率无性别差异,与其他部分种族存在差异.     

XPA单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性研究

目的：DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。该研究利用一种新型单核苷酸多态性（SNP）的检测方法，探讨DNA修复基因XPA的SNP与非小细胞肺癌（NSCLC）患者对顺铂（ciaplatin）或卡铂（carboplatin）为主的化疗方案敏感性的关系。方法：经病理学确诊的晚期NSCLC患者96例，采用顺铂或卡铂为主的方案化疗，2～3个周期后进行临床疗效评价。根据cDNA芯片原理制作一种目的基因芯片，利用双色荧光探针杂交进行咒蹦的A23G多态的基因分型，比较不同基因型对化疗敏感性的影响。组间比较采用χ^2检验，比值比（OR）及其95％可信区间（CI）由logistic回归模型计算。结果：成功进行基因分型，野生型、杂合型和突变型的叠加荧光分别显示为绿色、黄色和红色。携带咒蹦23A／A、A／G和G／G基因型的患者，化疗有效率（完全缓解＋部分缓解）分别为35．7％、46．9％和16．7％，差异有显著性统计学意义（P〈0．05）；携带G／G基因型患者的化疗失败风险是携带至少1个A等位基因（A／G和A/A基因型）个体的3．57倍；但G等位基因携带者的疗效与A等位基因携带者的相似，差异无统计学意义（30．9％ vs 41．7％，P=0．2045）。结论：该芯片检测方法准确、高通量且价格低廉，适用于大规模样本SNP调查；XPA基因多态与NSCLC患者对铂类药物化疗的敏感性相关。     

铂类化疗药物相关基因多态性对含奥沙利铂方案辅助化疗胃癌患者疗效的影响

目的 探讨铂类化疗药物相关基因多态性对接受含奥沙利铂方案辅助化疗胃癌患者的疗效预测价值.方法 经病理确诊的晚期胃癌患者126例,接受改良FOLFOX4方案化疗至少6周期.采用TaqMan探针实时荧光定量聚合酶链反应(PCR)法和直接测序法对患者外周血切除修复交叉互补基因1(ERCC1)第118位密码子,X线修复交叉互补基因1(XRCC1)第399位密码子,着色性干皮病基因D(XPD)第751位密码子和谷胱甘肽S-转位酶1(GSTP1)第105位密码子进行多态性分析;分析各基因型与胃癌患者生存时间的相关性.结果 126例胃癌患者基因型分析显示野生纯合子、杂合子和突变纯合子频率在ERCC1-118中为64.29%,28.57%和7.14%;在XRCC1-399中为56.35%,38.89%和4.76%;在XPD-751中为84.92%,15.08%和0,以及在GSTP1-105中为68.25%,30.60%和3.97%.单因素分析显示ERCC1-118,XRCC1-399和GSTP1-105单核苷酸多态性对患者无复发生存时间和总生存时间均有预测价值.多因素Cox风险模型分析提示ERCC1-118基因型对无复发生存时间(P＜0.001,HR=2.362;95%CI:1.458～3.827)和总生存时间(P=0.001;HR=2.388;95%CI:1.448～3.937)均具有预测价值,而XRCC1-399基因型仅对无复发生存时间有预测价值,XRCC1-399 A/A和A/G基因型患者疾病复发风险显著降低(P=0.031;HR=0.569;95%CI:0.341～0.949).结论 外周血ERCC1-118 C/C基因型(野生型)和XRCC1-399 A/G或A/A基因型(突变型)胃癌患者接受含奥沙利铂方案辅助化疗生存可能获益.

Abstract：

Objective To explore the predictive values of platinum-related genes in gastric cancer patients on oxaliplatin-based adjuvant chemotherapy. Methods A total of 126 gastric cancer patients received at least 6 cycles of modified FOLFOX4 adjuvant chemotherapy. Single nuclear polymorphisms (SNPs) in ERCC1 Asp118Asp, XRCC1 Arg399Gln, XPD Lys751Gln and GSTP1 Ile105Val were assessed with 5' nuclease allelic discrimination assay (TaqMan) by real-time polymerase chain reaction and direct sequencing. The genotypes were tested for an association with survivals in gastric cancer patients on an oxaliplatin-based adjuvant chemotherapy regimen. Results The genotypic analysis of all patients indicated the frequencies for the homozygous wild-type allele, heterozygous and homozygous polymorphic variant:64.29%, 28.57% and 7.14% for ERCC1-118; 56.35%, 38.89% and 4.76% for XRCC1-399;84. 92%, 15. 08% and 0 for XPD-751; and 68. 25%, 30. 60% and 3. 97% for GSTP1-105. Univariate analysis indicated that the ERCC1-118, the XRCC1-399 and the GSTP1-105 SNPs showed the predictive values for RFS ( relapse-free survival) (P ＜ 0. 001, P = 0. 001 and P ＜ 0. 001 respectively) and OS ( overall survival) (P ＜0. 001, P =0. 001 and P =0. 019 respectively). A multivariable analysis of Cox proportional hazard regression model suggested that ERCC1-118 had a significant predictive value for RFS (P＜0. 001,HR=2.362; 95%CI:1.458 -3.827) and OS (P=0.001; HR=2.388; 95%CI: 1.448 -3.937) and XRCC1-399 had only a significant predictive value for RFS. And XRCC1-399 (A/A + A/G) genotype could significantly decrease the recurrence risk of patients (P＜0. 001, HR =0. 569; 95% CI: 0. 341 -0. 949).Conclusion Gastric cancer patients with ERCC1-118 C/C genotype and XRCC1-399A/G or A/A genotype may benefit from an oxaliplatin-based adjuvant chemotherapy.     

XRCC1?PARP1和APE1多态性与晚期非小细胞肺癌铂类药物化疗敏感性的关系

目的:探讨碱基切除修复系统(BER) 3个重要基因——X线修复互补基因(XRCC1)?多(ADP核糖)聚合酶(PARP1)及脱嘌呤/脱嘧啶核酸内切酶(APE1)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者铂类药物化疗疗效的相关性?方法:对151例接受以铂类药物为基础化疗的晚期NSCLC患者进行临床疗效评价?采用TaqMan 探针法对XRCC1 G28152A(Arg399Gln)?XRCC1 C26304T (Arg194Trp)?PARP1 T2444C (Val762Ala)及APE1 T1349G (Asp148Glu)多态性位点进行基因型分析?比较不同基因型与铂类药物化疗效果之间的关系?结果:XRCC1 G28152A多态性与铂类化疗敏感性密切相关,GA杂合型患者临床受益率明显高于野生型,其化疗有效率为GG野生型的2.85倍(调整的OR=2.85, 95%CI:1.291~6.277, P < 0.05);至少携带1个变异等位基因A的患者(GA/AA)临床受益率为GG野生型携带者的2.48倍 (调整的OR=2.48, 95%CI:1.330~6.075, P < 0.05)?XRCC1 26304位点及PARP1 2444位点的突变纯合基因型携带者,其化疗有效率都明显下降,XRCC1 26304的TT基因型有效率是CT/CC基因型的0.36倍(调整的OR=0.36, 95%CI:0.040~3.298),PARP1 2444 CC基因型有效率是CT/TT基因型的0.37倍(调整的OR=0.37, 95%CI:0.118~1.170),但均未见有统计学差异?未发现APE1 T1349G多态性与铂类化疗疗效之间存在关联?结论:BER修复通路XRCC1 G28152A多态性与晚期NSCLC 患者铂类药物化疗临床受益相关,XRCC1 28152位点基因型检测有可能作为晚期NSCLC铂类化疗敏感性的预测指标?     

GSTP1多态性与乳腺癌新辅助化疗缓解和毒性反应差异相关

Background  Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individuval variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.

Methods  One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m² and CTX 600 mg/m² every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.

Results  Patients carrying GSTP1 ¹⁰⁵Ile/Val or ¹⁰⁵Ile/Ile genotype were more likely to have good response (OR, 0.40; 95% CI, 0.16−0.96; P=0.024) and light toxicity (OR, 0.35; 95% CI, 0.13−0.78; P=0.006) than those carrying ¹⁰⁵Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient’s age, tumor staging, menopause status, and dose intensity of the drugs.

Conclusion  GSTP1 polymorphism was associatiated with the chemotherapy response or adverse effects of EPI and CTX regimens.

     

GSTP1第5外显子多态性与COPD关系研究

目的研究谷胱甘肽S转移酶P1基因(GSTP1)第5外显子遗传多态(A/G)与中国西南汉族人群慢性阻塞性肺疾病(COPD)的相关性.方法采用聚合酶链反应-限制性片段长度多态分析法(PCR-RFLP),检测91例COPD患者与87例健康对照者GSTP1第5外显子各种基因型和等位基因频率,并分析其与COPD两种临床表型、肺损伤CT改变的关系.结果GSTP1第5外显子各种基因型频率及等位基因频率在COPD组与对照组间的分布差异无显著性(P>0.05),Ile105的频率在肺气肿型(红喘型)中显著高于支气管炎型(紫肿型)(P<0.05),携有Ile105的患者,其CT肺气肿损伤评分显著高于携有Ile105的患者(P<0.05).结论GSTP1第5外显子遗传多态(A/G)可能与中国西南汉族人群COPD易感性无关,但可能与COPD的临床表型、肺实质损伤有关.     

XPC Lys939Gln polymorphism is associated with the decreased response to platinum based chemotherapy in advanced non-small-cell lung cancer

Background Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer （NSCLC） patients, and genetic factors are thought to represent important determinants of drug efficacy. We prospectively assessed the status of the XPC Ala499Val and Lys939GIn gene polymorphisms and investigated whether these SNPs can predict the response to cisplatin/carboplatin-based regimens in advanced NSCLC patients in a Chinese population.Methods The treatment outcomes of 96 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of xeroderma pigmentosum group C （XPC） gene was genotyped by the 3-D polyacrylamide gel-based DNA microarray method.Results The distributions of XPC Lys939GIn genotypes differed significantly between the response group （complete ＋partial responses） and the non-response group （stable ＋ progressive disease; P=0.022）. The heterozygous A/C genotype carriers had a poorer response rate than the wild A/A genotype carriers in stage Ⅲ （OR, 0.074; 95% CI,0.008-0.704; P=0.023）. The XPC Ala499Val polymorphisms were not associated with response to platinum-based chemotherapy.Conclusion Polymorphisms of the XPC gene, Lys939GIn, may be a predictive marker of treatment response for advanced NSCLC patients in stage Ⅲ.     

贲门癌组织GSTM1,GSTT1和GSTP1基因多态变化

目的：探讨河南林州地区贲门癌组织中3种Ⅱ期代谢酶基因GSTMl，GSTTl及GSTPl基因多态性变化，进一步深入了解该地区贲门癌高易感性分子基础。方法：利用multlplex—PCR、PCR—RFLP检测19例手术切除贲门腺癌组织及72例正常对照组织(颊粘膜细胞和血细胞)中代谢酶基因GSTMl、GSTT1、GSTPl多态性改变。结果：贲门腺癌与正常对照组织中GSTMl纯合缺失基因型分别占37％和39％，该基因型未明显增加对贲门癌的易感性(0R＝0．69)；GSTT1纯合缺失基因型分别占53％和39％，该基因型可能与贲门癌易感性增高有关(0R＝2．38)；GSTPl的IIe／Val和Val／Val基因型合并在一起分别占26％和42％，Val等位基因能降低个体贲门癌的易感性(0R＝0．41)。结论：GSTMl基因多态对贲门癌易感性无明显影响，而GSTTl和GSTPl基因多态与贲门癌易感性有关。     

CYP1A1与GSTM1基因的多态性与西安地区食管癌的关系

目的 探讨细胞色素p450代谢酶1A1（CYP1A1）、谷胱苷肽转硫酶μ（GSTM1）基因多态性与西安地区食管癌的关系。方法 应用分子流行病学研究方法，调查分析了西安地区108例食管癌病例和101例对照CYP1A1与GSTM1基因多态性。结果 CYP1A1 Ile/Ile,Ile/Val,Val/Val基因型在病例和对照中分别为22.6%，43.4%，34.0%和30.7%，47.5%，21.8%；其中Val/Val基因型在两间差异显（P＝0.049）；GSTM1存在型、缺失型在病例，对照中分别为40.7%，59.3%和56.4%，43.6%差异显（P＝0.023）。结论 CYP1A1 Val/Val基因基因型（突变纯合子）与GSTM1的缺失与西安地区食管癌的遗传易感性有关。     

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease

Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% -20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione Stransferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113→His), exon 4 (His139→Arg) and GSTP1 polymorphism in exon 5 (Ile105→Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.Results The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32% ). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7. 09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers ( current smokers and exsmokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.Conclusions mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China.The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.