CYP1A1/GSTM1多态性和血浆锌/铜与非小细胞肺癌的关系研究
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摘要
目的:研究代谢酶基因CYP1A1、GSTM1的多态性与非小细胞肺癌(NSCLC)易感性的关系,为探索NSCLC发病机制及其诊断、防治理论提供新依据。方法:采用病例对照研究方法选择77例NSCLC患者和77例健康对照,通过统一设计的调查表收集环境暴露等流行病学资料,对病例和对照人群外周静脉血中DNA的CYP1A1、GSTM1基因多态性用PCR- RFLP方法测定。结果:工人和农民组NSCLC发病率高于其它人群(P<0.01),吸烟和NSCLC发生存在相关性(P<0.01),且肺癌患者中吸烟20年以上的频率高于20年以下的(P<0.05),NSCLC组接触粉尘、毒物、食用煎炸食品的频率明显高于对照组(P<0.01),而适当饮酒和饮用消毒自来水的频率NSCLC组明显低于对照组(P<0.01)。CYP1A1、GSTM1的基因型分布在病例组和对照组分布无统计学差异(P>0.05),CYP1A1与GSTM1的联合作用亦不明显,毒物接触、吸烟和CYP1A1非野生型之间,以及毒物接触和GSTM1缺失型之间,在NSCLC发病中可能存在轻度协同作用。结论: NSCLC的发生在不同职业之间存在一定差异,烟草暴露、接触粉尘和毒物、常食煎炸食品明显增加NSCLC危险性,食用消毒饮用水降低NSCLC危险性。CYP1A1、GSTM1基因单独作用与NSCLC关系不明显,吸烟及毒物接触和CYP1A1非野生型,及毒物接触GSTM1缺陷型可能存在轻度协同作用。
目的:探讨细胞色素P450(A)(CYP1A1)、谷胱甘肽硫转移酶M1(GSTM1),以及血浆微量元素锌、铜水平单独作用及其联合作用与非小细胞肺癌(NSCLC)发生危险的关系。方法:采用病例对照研究的方法,选择77例NSCLC患者和77例健康对照。用限制性片段长度多态性PCR技术(PCR-RFLP)检测CYP1A1的MspI多态性和GSTM1基因多态性,用电感耦合等离子体发射光谱法(ICP-AES)测定血浆微量元素锌、铜的水平。CYP1A1的MspI多态性及GSTM1多态性单独作用时与NSCLC危险性关系无统计学差异(P>0.05),且与肺癌的分型、分期、解剖部位无关,病例组血浆锌水平显著低于对照组(P<0.01),血浆铜显著高于对照组(P<0.01),以血浆锌≥117.0ng/dL且CYP1A1野生型基因或GSTM1功能型携带者为参照组(OR:1.00),则血浆锌<117.0ng/dL且携带CYP1A1突变型或杂合型基因者的OR为7.60(P<0.01),血浆锌<117.0ng/dL且携带GSTM1缺失型者的OR为8.55(P<0.01);以血浆铜<120.0ng/dL且CYP1A1野生型基因或GSTM1功能型携带者为参照组(OR:1.00),则血浆铜≥120.0ng/dL且携带CYP1A1突变型或杂合型基因者的OR为2.31(P>0.05),血浆铜≥120.0ng/dL且携带GSTM1缺失型者的OR为1.84(P>0.05)。结论:病例组血浆锌显著低于对照组,而铜水平显著高于对照组,CYP1A1、GSTM1基因单独作用时与NSCLC关系不明显;血浆锌水平与NSCLC发生呈负相关,而血浆铜水平则与NSCLC的发生呈正相关;血浆锌水平低与CYP1A1非野生型及GSTM1基因缺失型联合作用时,使NSCLC发生的危险显著增加,在NSCLC发生中可能存在协同作用。
Objective: To study the relationship among the genetic polymorphism of CYP1A1 and GSTM1, environment exposure and susceptibility to non- small cell lung cancer so as to explore the mechanism of lung cancer and the new basis of diagnosis, prevention and therapy for lung cancer. Methods: The case-control study was conducted among 77 non- small cell lung cancer cases and 77 healthy controls, data of environment exposure were collected by uniform questionnaire, the CYP1A1 and GSTM1 gene genetic polymorphisms were detected by the method of PCR-RFLP. Results: The NSCLC patients were more seen in worker and peasant groups,there was a statistical correlation in smoking and NSCLC(P<0.01), while the frequency of smoking more than 20 years is higher than that less than 20 years,there was a high frequency of dust and toxicant exposure in cases than in controls (P<0.01), and the same in deep-fry fats eating(P<0.01), by contrary, frequency of proper drinking and drinking sanitized water frequently was lower in cases(P<0.01). There was no statistical difference of GSTM1 null genotype frequency between case and control,the same as CYP1A1 (P>0.05), and the combinative effect between CYP1A1 and GSTM1 is not obvious,there was a low-grade synergistic interaction between toxicant and tobacco exposure with CYP1A1(I/V and V/V) genotype,and the same between toxicant esposure with GSTM1 null genotype. Conclusion: This study revealed there was some correlation beween NSCLC and occupation, smoking, dust, toxicant exposure and deep-fry fats eating significantly increase the risk of non- small cell lung cancer,drinking sanitized water frequently was associated with the decreased risk of lung cancer, there was no obvious effect in CYP1A1 or GSTM1 alone with lung cancer. maybe there was an elevated risk of lung cancer in CYP1A1(I/V and V/V) genotype with exposure to smoking and toxicant, and GSTM1 null genotype with exposure to toxicant.
Objective To study the correlation of polymorphism of CYP1A1 MspI,GSTM1 and plasma zinc,copper level in independently and in combination with the risk of NSCLC. Methods The case-control study was conducted among 77 lung cancer cases and 77 healthy controls.The CYP1A1 and GSTM1 genetic polymorphisms were detected by PCR-RFLP,while the plasma zinc,copper was determined by ICP-AES. Results There was no significant difference in polymorphism frequencies of CYP1A1 MspI or GSTM1 between the case and control.The genotypes were no significantly associated with the risk of lung cancer;Average plasma level of zinc or among the lung cancer cases was significantly lower than that among controls(P<0.01),while the lever of copper is higher;Comparing with those who had higher plasma zinc level(≥117.0ng/dL) with CYP1A1 I/I,the odds ratios of those who had lower plasma zinc(<117.0ng/dL) with CYP1A1 I/V or V/V was 7.60(P<0.01) and OR of those with GSTM1 null is 8.55(P<0.01);Comparing with those who had lower plasma copper level(<120.0ng/dL) with CYP1A1 I/I ,the odds ratios of those who had higher plasma copper(≥120.0ng/dL) with CYP1A1 I/V or V/V was 2.31(P>0.05) and OR of those with GSTM1 null is 1.84(P>0.05). Conclusion Polymorphism of CYP1A1 and GSTM1 was not associated with the risk of NSCLC;there was significant inverse association between plasma zinc level and this risk,while the copper is positive association.We suggested that there was a combined effect of polymorphism of CYP1A1 MspI,GSTM1 and palsma zinc level on NSCLC.
目的:探讨细胞色素P450(A)(CYP1A1)、谷胱甘肽硫转移酶M1(GSTM1),以及血浆微量元素锌、铜水平单独作用及其联合作用与非小细胞肺癌(NSCLC)发生危险的关系。方法:采用病例对照研究的方法,选择77例NSCLC患者和77例健康对照。用限制性片段长度多态性PCR技术(PCR-RFLP)检测CYP1A1的MspI多态性和GSTM1基因多态性,用电感耦合等离子体发射光谱法(ICP-AES)测定血浆微量元素锌、铜的水平。CYP1A1的MspI多态性及GSTM1多态性单独作用时与NSCLC危险性关系无统计学差异(P>0.05),且与肺癌的分型、分期、解剖部位无关,病例组血浆锌水平显著低于对照组(P<0.01),血浆铜显著高于对照组(P<0.01),以血浆锌≥117.0ng/dL且CYP1A1野生型基因或GSTM1功能型携带者为参照组(OR:1.00),则血浆锌<117.0ng/dL且携带CYP1A1突变型或杂合型基因者的OR为7.60(P<0.01),血浆锌<117.0ng/dL且携带GSTM1缺失型者的OR为8.55(P<0.01);以血浆铜<120.0ng/dL且CYP1A1野生型基因或GSTM1功能型携带者为参照组(OR:1.00),则血浆铜≥120.0ng/dL且携带CYP1A1突变型或杂合型基因者的OR为2.31(P>0.05),血浆铜≥120.0ng/dL且携带GSTM1缺失型者的OR为1.84(P>0.05)。结论:病例组血浆锌显著低于对照组,而铜水平显著高于对照组,CYP1A1、GSTM1基因单独作用时与NSCLC关系不明显;血浆锌水平与NSCLC发生呈负相关,而血浆铜水平则与NSCLC的发生呈正相关;血浆锌水平低与CYP1A1非野生型及GSTM1基因缺失型联合作用时,使NSCLC发生的危险显著增加,在NSCLC发生中可能存在协同作用。
Objective: To study the relationship among the genetic polymorphism of CYP1A1 and GSTM1, environment exposure and susceptibility to non- small cell lung cancer so as to explore the mechanism of lung cancer and the new basis of diagnosis, prevention and therapy for lung cancer. Methods: The case-control study was conducted among 77 non- small cell lung cancer cases and 77 healthy controls, data of environment exposure were collected by uniform questionnaire, the CYP1A1 and GSTM1 gene genetic polymorphisms were detected by the method of PCR-RFLP. Results: The NSCLC patients were more seen in worker and peasant groups,there was a statistical correlation in smoking and NSCLC(P<0.01), while the frequency of smoking more than 20 years is higher than that less than 20 years,there was a high frequency of dust and toxicant exposure in cases than in controls (P<0.01), and the same in deep-fry fats eating(P<0.01), by contrary, frequency of proper drinking and drinking sanitized water frequently was lower in cases(P<0.01). There was no statistical difference of GSTM1 null genotype frequency between case and control,the same as CYP1A1 (P>0.05), and the combinative effect between CYP1A1 and GSTM1 is not obvious,there was a low-grade synergistic interaction between toxicant and tobacco exposure with CYP1A1(I/V and V/V) genotype,and the same between toxicant esposure with GSTM1 null genotype. Conclusion: This study revealed there was some correlation beween NSCLC and occupation, smoking, dust, toxicant exposure and deep-fry fats eating significantly increase the risk of non- small cell lung cancer,drinking sanitized water frequently was associated with the decreased risk of lung cancer, there was no obvious effect in CYP1A1 or GSTM1 alone with lung cancer. maybe there was an elevated risk of lung cancer in CYP1A1(I/V and V/V) genotype with exposure to smoking and toxicant, and GSTM1 null genotype with exposure to toxicant.
Objective To study the correlation of polymorphism of CYP1A1 MspI,GSTM1 and plasma zinc,copper level in independently and in combination with the risk of NSCLC. Methods The case-control study was conducted among 77 lung cancer cases and 77 healthy controls.The CYP1A1 and GSTM1 genetic polymorphisms were detected by PCR-RFLP,while the plasma zinc,copper was determined by ICP-AES. Results There was no significant difference in polymorphism frequencies of CYP1A1 MspI or GSTM1 between the case and control.The genotypes were no significantly associated with the risk of lung cancer;Average plasma level of zinc or among the lung cancer cases was significantly lower than that among controls(P<0.01),while the lever of copper is higher;Comparing with those who had higher plasma zinc level(≥117.0ng/dL) with CYP1A1 I/I,the odds ratios of those who had lower plasma zinc(<117.0ng/dL) with CYP1A1 I/V or V/V was 7.60(P<0.01) and OR of those with GSTM1 null is 8.55(P<0.01);Comparing with those who had lower plasma copper level(<120.0ng/dL) with CYP1A1 I/I ,the odds ratios of those who had higher plasma copper(≥120.0ng/dL) with CYP1A1 I/V or V/V was 2.31(P>0.05) and OR of those with GSTM1 null is 1.84(P>0.05). Conclusion Polymorphism of CYP1A1 and GSTM1 was not associated with the risk of NSCLC;there was significant inverse association between plasma zinc level and this risk,while the copper is positive association.We suggested that there was a combined effect of polymorphism of CYP1A1 MspI,GSTM1 and palsma zinc level on NSCLC.
引文
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