谷胱甘肽硫转移酶M1和T1基因多态性与燃煤型砷中毒发病的关系

目的探讨谷胱甘肽硫转移酶M1和T1（GSTM1、GSTT1）基因多态性与燃煤污染型砷中毒发病风险的关系。方法采用多重等位基因特异聚合酶链反应技术检测贵州省130名燃煤型砷中毒患者及140名健康个体的GSTM1和GSTT1基因多态性，并分析不同基因型与砷中毒发病的关系。结果砷中毒病例组和对照组GSTT1纯合缺失基因型（GSTT1^（-/-））的频率分别为58．5％和45．0％，组间比较差异有统计学意义（Х^2=6．246，P〈0．05）；携带GSTT1^（-/-）基因型个体发生砷中毒的风险是携带GSTT1非纯合缺失基因型（GSTT1^（＋/＋）or（-/-））个体的2．18倍[比值比（OR）adj=2．18，95％可信区间（CI）：1．183～4．018]。砷中毒病例组和对照组间GSTM1纯合缺失基因型（GSTM1^（-/-））频率的差异无统计学意义（P〉0．05）。基因型联合分析显示：携带GSTM1^（-/-）和GSTT1^（-/-）联合基因型的个体，其砷中毒的发病风险显著增加（ORadj=2．931，95％CI：1．024～8．387）。结论GSTT1^（-/-）基因型可能是燃煤型砷中毒发生的重要危险内因之一。     

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。     

GSTT1及GSTM1与急性髓系白血病疗效及预后的研究

目的探讨谷胱甘肽硫转移酶(GSTs)家族中GSTT1和GSTM1基因多态性与急性髓系白血病(AML)疗效,药物不良反应与预后的关系。方法AML患者180例,用多重PCR方法检测GSTT1和GSTM1基因型,比较不同基因型患者的诱导治疗完全缓解(CR)率,药物不良反应发生率,总体生存期,无复发生存期和复发率。结果(1)GSTT1和GSTM1基因双非缺失型(double-present型)患者一疗程CR率高于GSTT1,GSTM1任一基因缺失型(null型),二者差异有统计学意义(P=0.013),GSTT1/GSTM1的null基因型患者发生不CR的危险度是double-present型患者的8.736倍(95%CI1.146~66.574)。GSTT1present型一疗程CR率高于GSTT1null型,二者比较亦有统计学意义(P=0.021,OR=2.572,95%CI1.136~5.826);(2)GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞<0.5×109/L及PLT<20×109/L持续时间差异无统计学意义,GSTM1null型患者发生AST异常的危险度是GSTM1present型的2.593倍(P=0.016,95%CI1.176~5.717);(3)double-present型总体和无复发生存期较GSTT1/GSTM1的null型患者长(平均总体生存期为68.4、38.5个月,P=0.028;平均无复发生存期为73.5、34.9个月,P=0.014),GSTT1null型患者无复发生存期短于GSTT1present型患者(平均无复发生存期为26.7、64.3个月,P=0.038),但二者总体生存期无统计学意义(P=0.653)。double-present型患者复发率显著低于GSTT1/GSTM1的null型患者(13.3%、35.6%,P=0.019)。结论GSTT1,GSTM1基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性,GSTT1和GSTM1基因型有助于指导AML患者个体化治疗方案的制定。     

谷胱甘肽S-转移酶M1、T1基因多态性与骨肉瘤易感性的Meta分析

目的 定量分析谷胱甘肽S-转移酶M1、T1(GSTM1、GSTT1)基因多态性与骨肉瘤易感性的关系.方法 检索PubMed、Embase、CNKI、维普、万方数据平台从建库到2013年2月的文献,对符合本实验纳入标准和排除标准的随机对照临床研究,运用RevMan5.0.0软件进行Meta分析.结果 共纳入3篇文献,累计样本量为914例,其中病例组202例,对照组712例.Meta分析见GSTTI位点的多态性与骨肉瘤易感性有显著关联,而GSTM1和骨肉瘤无显著关联(基因型GSTM1空白对GSTM1非空白:OR=1.21,95％ CI:0.86～1.70,P=0.27;基因型GSTT1空白对GSTT1非空白:OR=1.58,95％ CI:1.11 ～2.25,P=0.01).结论 GSTT1基因多态性与骨肉瘤相关,GSTT1空白基因型可能增加骨肉瘤的发病.     

中国人谷胱甘肽-S-转移酶M1和T1基因多态性与原发性肝细胞癌的易感性

目的 探讨中国人群谷胱甘肽-S转移酶(GST) M1和T1基因多态性与原发性肝细胞癌遗传易感性的关系. 方法 通过检索PubMed和中国知网等数据库中的谷胱甘肽-S-转移酶基因多态性与原发性肝细胞癌的25篇文献,针对累计病例2788例和正常对照5548例进行Meta分析和关联性研究.对数据进行皮尔逊x2检验和异质性检验.结果 GSTM1、GSTT1空白基因型与原发性肝细胞癌易感性有统计学意义,病例对照的皮尔逊x2检验P值分别是1.8×10-11和4.6×10-11,比值比(OR值,95％ CI)分别为1.67 (1.39 ～ 2.01)和1.59 (1.29 ～ 1.96).GSTM1和GST1的交叉分析,两者均为空白基因型的OR值(95％ CI)为3.34 (2.23 ～ 5.00),明显高于GSTM1和GSTT1中有一个空白基因型的OR值,相对易感性更大;两者至少有一个空白基因型比两者均为非空白基因型能提高原发肝细胞癌发病的危险性,OR值(95％CI)是2.52 (1.87 ～ 3.38). 结论 谷胱甘肽-S-转移酶GSTM1、GSTT1的空白基因型分别是中国人群原发性肝细胞癌的易感因素,并且GSTM1和GSTT1两者联合对原发性肝癌有协同易感作用.     

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。     

细胞色素P4501A1基因多态性和谷胱甘肽硫转移酶基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系

目的 探讨细胞色素P4501 A1(CYP1A1)MspI位点多态性、谷胱甘肽硫转移酶(GSTM1)基因缺失及烹调油烟暴露与非吸烟女性肺癌易感性的关系.方法 2009年3一12月选择中南大学湘雅医院女性非吸烟的原发性肺癌患者及对照各160例,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)及聚合酶链反应(PCR)技术分别检测CYP1A1 MspI多态性及GSTM1基因型,分析基因的多态性、分型及烹调油烟暴露与肺癌遗传易感性的关系.结果 肺癌组及对照组烹调油烟暴露的频率分别为51.9%(83例)及33.7%(54例),差异有统计学意义(x2=10.734,P＜0.01);肺癌组MspI位点突变的等位基因频率为44.4%(71例),高于对照组(36.9%,59例),差异无统计学意义(X2=3.731,P＞0.05);携带突变型或杂合型基因同时又有油烟暴露个体患肺癌的风险明显增高,OR(odds ratio)值分别为3.032(95%CI为1.291～7.124)和2.769(95%CI为1.341～5.552);肺癌组GSTM1缺失型的频率为58.1%(93例),与对照组(45.0%,72例)比较,差异有统计学意义(X2=0.518,P＜0.05),GSTM1缺失型的个体患肺癌的风险明显增高,OR值为1.697(95%CI为1.090～2.640);携带GSTM1缺失型且有烹调油烟暴露的个体肺癌的易感性明显增加,其OR值为3.617(95%CI为1.899～6.891);GSTM1缺失型与CYP1A1 MspI杂合型或突变型联合作用时,个体患肺癌的风险亦增高,OR值分别为1.966(95%CI为1.007～3.836)和2.402(95%CI为1.023～5.640),差异明显.结论 烹调油烟暴露是非吸烟女性肺癌的危险因素;CYP1A1 MspI基因多态性与烹调油烟联合作用可增加肺癌发病的风险;GSTM1基因缺失可能是非吸烟女性肺癌的遗传易感因素,其与烹调油烟暴露联合作用可明显增加肺癌发病的风险,且GSTM1基因缺失与CYP1A1基因多态性存在交互作用.     

N-乙酰基转移酶2及谷胱甘肽S转移酶M1基因多态性与抗结核药物性肝损伤的关系研究

目的 研究药物代谢酶NAT2、GSTM1、GSTT1的基因多态性与抗结核药物肝损伤的关系,阐明抗结核药物性肝损伤（antituberculosis drug induced liver injury,ATDILI）的分子机制.方法 解放军第三○九医院结核科2008-2009年度住院初治结核病患者208例,具有明确抗结核药物性肝损伤发生的患者为肝损伤组（共101例）,无抗结核药物性肝损伤发生的患者为对照组（共107例）,通过PCR扩增产物直接测序的方法分析两组的NA T2基因多态性并分型.通过多重PCR方法检测两组患者GSTM1、GSTT1是否存在基因型缺失.以SPSS12.0软件进行x2检验处理,比较两组之间各基因型分布频率的差异,并计算各基因型风险系数（odds ratio,OR值）及95％可信区间（95％ CI）,分析疾病与基因的关联强度.结果 （1）肝损伤组患者中,39.6％ （40/101）为NAT2慢乙酰化基因型;对照组中,12.2％（13/107）为NA T2慢乙酰化基因型.NA T2慢乙酰化基因型者发生抗结核药物性肝损伤的风险系数（OR值）为4.74（95％CI＝2.42～9.28;x2 =20.62,P＜0.05）.（2）肝损伤组中,GSTM1缺失基因型占63.4％（64/101）,对照组GSTM1缺失基因型占51.4％（55/107）;两组比较GSTM1缺失基因型发生药物性肝损伤的OR值偏高（但无统计学意义）,为1.64（95％CI＝0.94～2.84,x2＝3.038,P＞0.05）.肝损伤组中,GSTT1缺失基因型占47.5％（48/101）,对照组GSTT1缺失基因型占45.8％（49/107）,两组比较OR值接近,为1.07（95％CI＝0.62～1.85,x2＝0.063,P＞0.05）.（3）肝损伤组中同时具有NA T2慢乙酰化基因型及GSTM1缺失基因型的患者29例,对照组5例,发生抗结核药物性肝损伤的风险系数OR值高达10.21（95％CI＝3.87～26.96,x2＝20.62,P＜0.005）.结论 NAT2基因的慢乙酰化基因型及GSTM1缺失基因型可能与ATDILT有关.     

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.     

代谢酶基因GSTM1和广西人群胃癌遗传易感性的关系

目的探讨代谢酶基因GSTM1多态性与广西地区人群胃癌遗传易感性之间的相关性。方法采用PCR技术检测广西地区121例胃癌患者和138例健康人的GSTM1基因多态性的分布频率,分析其与广西地区胃癌遗传易感性之间的相关性以及与吸烟、饮酒在胃癌易感性中的交互作用。结果胃癌组GSTM1（-）基因型频率（54．5％）显著高于对照组（39．1％）（X^2=6．140,P=0．013）。携带GSTM1（-）基因型的个体患胃癌的风险是携带GSTM1（＋）基因型个体的2．13倍（95％CI=1．079-1．831,P=0．013）。在吸烟者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险明显增加（OR=3．247,95％CI=1．067—2．328,P=0．015）。其增加程度远远高于总的胃癌风险（OR=2．129）。在饮酒者中,携带GSTM1（-）基因型的个体较携带GSTM1（＋）基因型的个体患胃癌的风险亦明显增加（OR=3．117,95％CI=1．020—2．863,P=0．033）。其增加程度远远高于总的胃癌风险（OR=2．129）。结论GSTM1（-）基因型显著增加广西地区人群患胃癌的风险,且显著增加吸烟、饮酒者患胃癌的风险。     

Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease

Cancer studies suggest that the null polymorphisms of glutathione S-transferase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has not been studied in humans. A case-cohort study was conducted to test the hypotheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n=400) accrued during 1987-1993 and a cohort-representative sample (n=924) were selected from a biracial cohort of 15792 middle-aged men and women in four US communities. A significantly higher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in whites (GSTM1-0=47.1%, GSTT1-0=16.4%) than in African-Americans (AAs) (GSTM1-0=17.5%, GSTT1-0=25.9%). A smoking-GSTM1-0 interaction for the risk of CHD was statistically significant on an additive scale, with ever-smokers with GSTM1-0 at a approximately 1.5-fold higher risk relative to ever-smokers with GSTM1-1 and a approximately 2-fold higher risk relative to never-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked >/=20 pack-years and GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and >/=20 pack-years of smoking was approximately three times greater than the risk given exposure to >/=20 pack-years of smoking alone, and approximately four times greater than the risk given exposure to GSTT1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT1 suggests that chemicals in cigarette smoke that are substrates for glutathione S-transferases may be involved in the etiology of CHD.     

Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Glutathione-S-transferase (GSTM1, GSTT1) and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, largescale case-control study including 2213 GCs, 1829CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using realtime PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls.Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: a meta-analysis

There were some studies on the associations between Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) polymorphisms and cervical cancer (CC) risk, but the results were inconsistent. Thus, a meta-analysis was performed. The electronic databases PubMed, Science Direct, CBM, and CNKI were searched for possible studies. Finally, 16 studies (1,627 cases and 2,161 controls) were included. For the GSTM1 and GSTT1 polymorphisms, the unadjusted odds ratios (OR) and 95% confidence intervals (95% CI) from each study were used to estimate summary OR. Subgroup analyses by ethnicity and histological type of CC were also performed. For the GSTM1 polymorphism, the null genotype of GSTM1 was associated with an increased CC risk in total population (OR=1.32, 95% CI=1.06-1.66). Similar association was found in Asians (OR=1.47, 95% CI=1.11-1.94), but not in Caucasians (OR=0.96, 95% CI=0.73-1.27). For the GSTT1 polymorphism, the null genotype of GSTT1 was not statistically significantly associated with CC risk in total population (OR=1.36, 95% CI=0.97-1.90). This result was also found in Asians (OR=1.27, 95% CI=0.87-1.85) and Caucasians (OR=1.09, 95% CI= 0.66-1.79), but not in Latinos (OR=4.58, 95% CI= 2.04-10.28). For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk in total population (OR=1.77, 95% CI= 1.14-2.75), and all the six studies were from Asia. For subgroup analyses by histological type of CC, the three aspects of the analyses above were all not significantly associated with CC risk in squamous cell carcinoma and adenocarcinoma, respectively. The null genotype of GSTM1 and the dual null genotypes of GSTM1/GSTT1 were risk factors in CC, and the null genotype of GSTT1 was not associated with CC risk.     

Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1 polymorphisms, and congenital heart disease

Congenital heart defects (CHDs) are the most prevalent of all birth malformations arising from the complex interplay of environmental exposures and genes. Modifiable environmental risk factors are still largely unknown, especially for paternal exposure. The aim of the present study was to examine the association between the environmental exposures of both parents and CHD risk and to explore the modification effect of metabolizing gene polymorphisms in children who lack the genetic capacity to produce the glutathione S-transferase (GST) GSTM1 and GSTT1 enzymes. A total of 330 parents of a child with CHD and 330 parents of a child without any congenital malformations were compared in terms of lifestyle habits and toxicant exposure. GST gene polymorphisms were investigated in 180 patients with CHD (104 males, age 4.9 ± 5.8 years). Paternal smoking (≥15 cigarettes/day) was significantly associated with CHD risk (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.5, p = 0.002). Both maternal (OR 2.6, 95% CI 1.6 to 4.2, p <0.0001) and paternal (OR 2.5, 95% CI 1.6 to 3.8, p <0.0001) occupational/environmental exposures increased the risk of CHD. Also, a significant additive risk (OR 4.5, 95% CI 2.5 to 8.3, p <0.0001) was found when both parents were exposed to toxicants. Both maternal (OR 3.6, 95% CI 1.1 to 11.2, p = 0.03) and paternal (OR 3.3, 95% CI 1.0 to 10.8, p = 0.03) exposure to toxicants increased the CHD risk in children who carried the combined null GST genotypes. The effect for the combined null GST genotypes was also stronger (OR 6.5, 95% CI 1.5 to 28.0) when both parents were exposed. In conclusion, paternal smoking and exposure to toxicants for both parents affect the risk of children with CHD. Polymorphisms in GST genes can modify a person's risk of toxicant exposure-induced disease.     

Combined GSTM1 and GSTT1 null genotypes are associated with a lower risk of papillary thyroid cancer

Individual susceptibility to cancer is influenced by polymorphisms of genes encoding drug-metabolizing enzymes such as the glutathione S-transferases (GST). The null polymorphisms of the GSTM1 and GSTT1 genes have been associated to a modified risk of several cancers but studies of thyroid cancer have produced conflicting results. The aim of this study was to investigate the relationship between these polymorphisms and the risk of papillary thyroid cancer (PTC). A total of 188 patients with PTC and 247 controls were genotyped using a PCR-based assay. Odds ratios (OR) and 95% confidence intervals (CI) for each homozygous null genotype were determined. The frequency of each of the GSTM1 and GSTT1 null genotypes did not differ significantly between patients and controls (OR=0.83, 95%CI: 0.56-1.21; p=0.328; and OR=0.66, 95%CI: 0.39-1.12; p=0.123, respectively), but the frequency of individuals that had the combined GSTM1 null/GSTT1 null genotypes was significantly lower in the patient group (OR=0.50, 95%CI: 0.26-0.97; p=0.040). The GSTM1 null genotype was associated with a lower risk of advanced cancer stages (III/IV) (OR=0.50, 95%CI: 0.26-0.96; p=0.036) and the GSTT1 null genotype was associated with a lower risk of the follicular variant of PTC (OR=0.31, 95%CI: 0.10-0.97; p=0.044). These results suggest that GSTM1 and GSTT1 null genotypes are weak, yet possible, modifiers of the risk of PTC. This protective effect may be due to a role of the GSTM1 and GSTT1 encoded enzymes in the metabolic activation of putative thyroid carcinogens or in other pathways involved in thyroid carcinogenesis.     

Vegetable／fruit, smoking, glutathione S-transferase polymorphisms and risk for colorectal cancer in Taiwan

AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking. METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736 sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking. RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64). These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR=0.17 and 0.21 respectively. CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/ fruit-related colorectal cancer risk, particularly in men of no smoking history.     

Genetic polymorphism at GSTM1 and GSTT1 gene loci and susceptibility to oral cancer

GSTs are phase II enzymes which are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and therefore may play an important role in modulating susceptibility to tobacco related cancers. This study evaluates the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci on susceptibility to oral cancer. The genotyping was based on multiplex PCR assay that identified the GSTM1 and GSTT1 null (-/-) genotypes but didn't distinguish homozygous wild type+/+ and heterozygous +/- individuals. Genomic DNA was isolated from cases with oral cancer (n=40) and normal controls (n=87). The prevalence of the GSTM1 null genotypes was 29/87 (33.3%) and 21/40 (52.5%) in controls and oral cancer cases, respectively but the differences were not significant (OR=2.2; 95%CI=0.96-5.1; p=0.06). The frequency of homozygous GSTT1 null genotype in cancer cases was 17/40 (42.5%) as compared to 13/87 (14.94%) in controls and the differences were highly significant (OR=4.2; 95%CI=1.64-10.9; p=0.0002). Oral cancer cases had higher proportion of both GSTM1 and GSTT1 null genotypes as compared to controls but the differences were not statistically significant (OR=2.9; 95%CI=0.71-11.9; p=0.17). When individuals were categorized into two groups, no differences were observed for GSTM1 null genotype frequencies in control and cancer cases (OR=2.9; 95%CI=0.9-9.6; p=0.08) (OR=1.6; 95%CI=0.44-6.1; p=0.58) in <=50 yrs and >50 yrs of age groups. Significant differences between control and cancer cases were observed for GSTT1 null genotypes both in <=50 yrs and >50 yrs of age groups (OR=4.0; 95%CI=1.1-15.0; p=0.03) (OR=4.5; 95%CI=0.97-22.29; p=0.05), respectively. The effect of smoking on GSTM1 null individuals was not found significant (OR=1.0; 95%CI=0.19-4.86; p=0.75) but it was significant in case of GSTT1 null individuals (OR=6.33; 95%CI=1.0-44.1; p=0.02). Our results thus suggest that GSTT1 gene polymorphisms modulate susceptibility to tobacco-related cancer of the oral cavity.     

Glutathione-S-transferase genotypes, smoking, and their association with markers of inflammation, hemostasis, and endothelial function: the atherosclerosis risk in communities (ARIC) study

Recent epidemiologic studies suggest that polymorphisms of glutathione-S-transferases M1 and T1 (GSTM1/GSTT1) modify the effects of cigarette smoking on risk of coronary heart disease (CHD). Since GSTs are able to detoxify numerous toxic compounds and products of oxidative stress, it is possible that GST genotypes may also modify the capacity of smoking to invoke a chronic inflammatory response. A cross-sectional analysis, using a subset of participants (n = 989) in a large (n = 15, 792) biracial cohort, was used to evaluate levels of nine markers of inflammation, hemostasis, and endothelial function by different combinations of GST genotypes and cigarette smoking status. Participants with the GSTM1 null (GSTM1-0) genotype and > or = 20 pack-years of smoking had the highest mean levels of CRP, fibrinogen, von Willebrand factor, ICAM-1, and VCAM-1 and lowest mean levels of albumin compared to other combinations of genotype and smoking. However, a formal test for interaction between GSTM1 genotype and smoking was statistically significant only for albumin. By contrast, participants who had the functional GSTT1 genotype (GSTT1-1) and smoked > or = 20 pack-years had the highest mean levels of only CRP and fibrinogen. The results of this study provide some limited evidence that GSTM1 and GSTT1 polymorphisms modify the effect of smoking on inflammation, hemostasis, and endothelial function.