细胞色素P450 2D6与吸烟所致肺癌易感性的关系研究

细胞色素P450 2D6(CYP2D6)是肝脏中重要的Ⅰ相代谢酶,参与烟草中特异性亚硝胺类如4-甲基亚硝胺-1,3-吡啶基-1-丁酮(NNK)及烟碱的代谢,可能涉及吸烟引起的肺癌变过程。对其生物学特性、结构功能和基因多态与肺癌易感性的关系等方面的研究,有助于深入理解CYP2D6基因多态性对个体肺癌易感性的重要影响,并从基因-环境交互作用的角度,更好地进行危险度评价。     

细胞色素P450与肺癌关系研究进展

细胞色素P450(cytochrome P450,CYP450)是广泛存在于生物体内的一组含亚铁血红素蛋白,结构和功能相关的超家族基因编码的同工酶,相对分子质量50 kD,因它与一氧化碳的结合物在450 nm附近有特征吸收而得名.     

细胞色素P450 2E1活性的测定方法

细胞色素P450(cytochmme P450)是主要的肝细胞Ⅰ相代谢酶之一,其亚家族细胞色素：P450 2E1(CYP2E1)在外来化学物的代谢活化中起重要作用,CYP2E1活性的高低与毒物对机体的最终毒性大小直接相关。多年来,体内CYP2E1活性的测定一直是国内外学者颇感棘手的问题。本文从体外、体内以及淋巴细胞中CYP2E1活性的测定等几方面对该问题进行综述。     

细胞色素P450基因多态及血清硒与肺癌的关系

目的 探讨细胞色素P450(A)(CYP1A1)的MSPI基因多态性、血清硒水平单独作用以及联合作用与肺癌发生危险性的关系。方法 采用成组病例一对照研究方法，病例58例，对照62例。用PCR-RFLP技术测定CYP1A1的MsPI多态性。用双道原子荧光光度计(GHAFS)测定血清硒水平。结果 CYP1A1的MsPI基因多态性单独作用时与肺癌危险性关系无显著性差异；病例组血清硒水平显著低于对照组(P=0．001)：以血清硒水平大于等于0．109mg／L。携带CYP1A1野生型者为参照组，则血清硒水平低于0．109mg／L且携带CYPlAl突变型或杂合型或携带野生型者OR分别为9．00(P=0．006)，3．94(P=0．195)，5．40(P=0．036)，而血清硒水平大于等于0．109mg／L携带突变型或携带杂合型者OR分别为1．69(P=0．500)，1．13(P=0．705)。结论 CYP1A1基因多态性单独作用时与肺癌发生无显著相关，血清硒水平与肺癌发生呈负相关；CYP1A1基因多态性与血清硒水平联合作用时明显提高肺癌发生的危险性，在肺癌发生中存在协同作用。     

细胞色素P450 2E1基因多态性与小细胞肺癌相关性分析

小细胞肺癌在肺癌中恶性度极高。细胞色素P450 2El基因(CYP2E1)作为一种重要的I相代谢酶参与多种致癌物的代谢,其位点多态性可影响自身表达…。本研究采用病例对照研究方法,分析CYP2E1—1239位点多态性与小细胞肺癌发病风险的关系。     

铸造工人吸烟、多环芳香烃摄取和细胞色素P450 IA_2活性的交互作用

以前的研究证实铸造工人患肺癌的危险性增加。为探讨铸造工人吸烟与致癌物质多环芳香烃(PAHs)摄取以及对PAHs有激活作用的细胞色素P450IA_2活性的交互作用,作者进行此项研究。研究对象为丹麦农村一家铁器铸造厂的45名(男35,女10)作业工(接触组)和一家自来水净化厂无PAHs职业接触史的52名男性工人(对照组),2组受试者年龄相似。让受试者自己填写调查表,内容包括职业史、吸烟饮酒情况、呼吸系统症状及用药史。根据环境监测资料将接触组进一步分为高接触组(PAHs均值为6.41μg/m~3,芘均值为0.28μg/m~3,可吸性     

细胞色素P450的研究进展

细胞色素Ｐ４５０（ＣＹＰ４５０）是微粒体混合功能氧化酶中最重要的一族氧化酶，在生物体内分布广泛。ＣＹＰ４５０ 参与多种外源性化合物代谢、内源性物质生成，尤其是影响肿瘤的药物治疗。对ＣＹＰ４５０ 的研究已从最初的功能和定位，深入到它的同功酶的多态性、诱导机制、分子调控机制等。本文将就这些方面的研究进展作一综述。     

细胞色素P450 1A1和2D6基因多态性与慢性苯中毒的危险性

目的 探讨细胞色素P450 1A1和2D6基因多态性与慢性苯中毒易感性的关系.方法 采用病例-对照研究,选择152名苯中毒工人为病例组,152名接触苯而无中毒表现的工人为对照组.采用限制性片段聚合酶链反应（PCR-RFLP）技术检测CYP1A1基因3＇端非编码区MspⅠ和CYP2D6第1外显子c.188位点、g.212位点多态性.结果 携带CYP1A1 MspⅠT/T基因型的个体发生苯中毒的危险性是携带有CYP1A1 Msp Ⅰ T/C或C/C基因型的个体的1.32倍（95%CI：1.05～1.65,P=0.02）;在不吸烟的人群中,携带CYP1A1 MspⅠ T/T基因型的个体发生苯中毒的风险性是携带T/C或C/C基因型的个体的1.56倍（95%CI：1.15～2.12,P=0.003）;携带有CYP2D6 c.188 C/C或C/T基因型个体发生苯中毒的危险性是携带有CYP2D6 c.188 T/T基因型的个体的1.23倍（95%CI：1.05～1.42,P=0.01）,在不吸烟的人群中,携带CYP2D6 c.188 C/C或C/T基因型个体发生苯中毒的危险性是携带有CYP2D6 c.188 T/T基因型的个体的1.23倍（95%CI：1.04～1.47,P=0.01）.未发现研究对象的CYP2D6g.212位点存在多态性.结论 携带CYP1A1 Msp ⅠT/T基因型、CYP2D6 c.188 C/C和C/T基因型个体对苯中毒可能易感.     

细胞色素P450基因多态性与重度牙周炎的关系

[目的]探讨细胞色素P450（cytoehrome P450，CYP450）基因多态性与重度牙周炎易感性关系。[方法]采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，对河南地区66例重度牙周炎病例和40例正常对照的CYP2E1基因型进行检测。[结果]在重度牙周炎病例组和对照组中，Rsa Ⅰ识别的CYP2E1野生型（C1／C1）基因频率分别为59．1％和。60．0％.（P〉。0．05）；Dra Ⅰ识别CYP2E1野生型（DD）基因频率分别为51．5％和37．5％，Msp Ⅰ识别的CYP1A1突变纯合型（m2／m2）基因频率分别为。27．3％和12．5％，差异均无统计学意义（OR值分别为0．963、1．174和0．381：P分别为0．926、0．689和0．0737）。[结论]CYP2E1基因Rsa Ⅰ、Dra　Ⅰ多态性和CYP1A1基因Msp Ⅰ多态性与河南地区重度牙周炎易感性可能无关。     

GSTM1和CYP2D6基因多态性与肺癌敏感性的关系

采用病例－对照研究方法,应用ＰＣＲ技术检测５９例肺癌患者、５９例住院对照和７３例健康对照的ＧＳＴＭ１（－）型频率,分别为５７．６％、４９．２％和４９．３％,差异无显著性;经病理分型后,在腺癌中ＧＳＴＭ１（－）的频率（７６．９％）高出２个对照组（平均４９．２％）３．４２～３．４５倍,差异有显著性（Ｐ＝０．０１５～０．０１７）,提示ＧＳＴＭ１（－）型可能是肺腺癌的敏感性标记。应用ＰＣＲ－ＲＦＬＰ技术检测肺癌组和住院对照组的ＣＹＰ２Ｄ６Ｃｈ（Ｔ１８８／Ｔ）基因型频率,分别为３５．６％和４７．５％,差异无显著性;经吸烟指数分层后在不吸烟者中,肺癌组的Ｔ１８８／Ｔ型频率（１９％）显著低于住院对照组（４７．１％）,ＯＲ＝３．７８,Ｐ＝０．０３６,提示在不吸烟者中Ｔ１８８／Ｔ型可能是肺癌的一个保护因子。联合分析未见ＧＳＴＭ１和ＣＹＰ２Ｄ６Ｃｈ有协同关系。     

细胞色素P450基因多态与肿瘤易患性的关系

本文就近年来对CYP基因、基因的多态性与外源性物质代谢的关系,以及CYP 1A1、2D6、2E1和2C19与肿瘤易患性的关系等研究进展作了综述。     

细胞色素P450基因多态与肿瘤易患性的关系

本文就近年来对ＣＹＰ基因,基因的多态性与外源性物质代谢的关系,以及ＣＹＰ １Ａ１,２Ｄ６,２Ｅ１和２Ｃ１９与肿瘤易患性的关系等研究进展作了综述。     

细胞色素P450 2C19基因多态性研究进展

细胞色素P4502C19(CYP2C19)是1种十分重要的药物代谢酶,主要存在于肝脏微粒体内,许多内源性底物、环境污染物以及临床上大约2%的药物均由其催化代谢^〔1〕。CYP2C19主要存在于肝微粒体中,位于第10号染色体上(10q 24·1~24·3)。CYP2C19由490个氨基酸组成,分子量为55 933,其全部顺序包括9个外显子和5个内含子,序列均已清楚^〔2〕。因其活性存在明显个体差异,对不同个体的药物治疗作用和不良反应及药物毒性产生重要影响,本研究主要对CYP2C19基因结构、基因多态性及其与药物代谢的关系的研究进展进行综述。     

吸入甲醛对大鼠肺细胞色素P450活性的影响

本文目的在于了解吸入甲醛(HCHO)对肺微粒钵P450的影响。实验用体重为150～175g的雄性SD大鼠,随机分组。设1个对照组以及0.5(居民吸入上限)、3.0(工人职业接触上限)和15ppm(致癌浓度) 3个实验组。各组设四种实验时间点(1日、4日、12周和24周)。每日     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.