毒物代谢酶基因多态性与结肠腺癌易感性关联

目的　探讨谷胱甘肽S 转移酶 (GST)M 1、T1和N 乙酰化转移酶 1(NAT1)基因多态与散发性结肠腺癌 (SCRAC)遗传易感性的关联。方法　应用PCR 限制性片段长度多态性 (RFLP)及多重PCR技术检测GSTM 1、GSTT1和NAT1基因多态性。结果　GSTM1、GSTT1空白基因型在对照组与病例组之间的频率比较 ,差异均无显著性 ,而NAT1 10的频率差异有显著性 (2 7.8%∶4 2 .3% ,P <0 .0 5 )。不同临床特征、老年或非老年SCRAC与对照组GSTM 1空白基因型的频率比较 ,差异均无显著性 ;GSTT1空白基因型在SCRAC远端 (6 6 .2 % ,P <0 .0 5 )、DukesC期 (80 .8% ,P <0 .0 1)及低分化(77.1% ,P <0 .0 1)中的频率均显著高于对照组 (4 7.5 % )。NAT1 10在不同部位SCRAC与对照组之间的频率差异无显著性 ,SCRAC在老年 (5 2 .7% ,P <0 .0 1)、DukesC期 (5 3.8% ,P <0 .0 5 )及中分化(5 4 .2 % ,P <0 .0 1)中的频率均显著高于对照组。结论　GSTT1空白基因型与远端SCRAC易感性有关 ,癌肿多处于DukesC期 ,多呈低分化腺癌 ;NAT1 10与SCRAC的遗传易感性有关 ,癌肿多见于老年患者 ,多处于DukesC期 ,多呈中度分化腺癌。     

老年散发性大肠腺癌患者GSTT1基因多态性及其临床特征分析

目的　探讨谷胱甘肽 S 转移酶T1(GSTT1)基因多态性与老年人散发性大肠腺癌易感性及其临床特征。　方法　应用多重聚合酶链反应技术检测GSTT1基因多态性。　结果　GSTT1空白基因型频率在老年散发性大肠腺癌患者 (6 6 7% )、老年远端散发性大肠腺癌患者 (75 5 % )与老年对照组 (5 1 8% )之间的差异均有显著性 (前者 χ2 =4 2 7,P <0 0 5 ;后者 χ2 =7 93,P <0 0 1) ;老年中度分化性大肠腺癌患者 (80 7% )GSTT1空白基因型的频率明显高于老年对照组 (χ2 =8 30 ,P <0 0 1) ;不同临床分期的老年大肠腺癌患者与老年对照组比较 ,GSTT1空白基因型的频率差异均无显著性。　结论　GSTT1空白基因型与老年人散发性大肠腺癌的易感性有关 ,肿瘤多位于大肠远端 ,呈中度分化性腺癌。     

N-乙酰化转移酶1基因分型及其与散发性大肠腺癌易感性

目的　分析N 乙酰化转移酶 1 (NAT1 )各等位基因型及其与散发性大肠腺癌 (SCRAC)易感性之间的关联。方法　应用聚合酶链反应 (PCR) 限制性片段长度多态性分析 (RFLP)及多重PCR技术 ,检测中国湖北地区汉族无血缘关系的健康人 1 0 1例、SCRAC患者 1 0 4例的NAT1基因多态性。结果　 (1 )NAT1等位基因 1 0 (NATI 1 0 )频率在SCRAC患者与健康人之间及老年SCRAC患者与健康人之间的差异均有显著性 (前者P <0 0 5 ,OR =1 91 ,95 %CI=1 1～ 3 4;后者P <0 0 1 ,OR =2 91 ,95 %CI =1 48～ 5 90 ) ;在近端或远端SCRAC与健康人之间的差异无显著性 (P >0 0 5) ;(2 )DukesⅡ期、Ⅲ和Ⅳ期分别与健康人相比 ,其NAT1 1 0的频率差异均有显著性 (前者P <0 0 5 ,OR =2 48,95 %CI=1 1 8～ 5 2 0 ;后者P <0 0 5 ,OR =3 0 4 ,95 %CI =1 2 8～ 7 2 0 )。结论　NAT1 1 0与SCRAC易感性有关 ,其患者肿瘤浸润、转移早 ,与癌灶部位无关 ;是否与老年SCRAC易感性有关尚不清楚     

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.     

谷胱甘肽转硫酶T1、M1和P1基因多态与反流性食管炎易感性

目的　研究谷胱甘肽转硫酶 (GSTs)T1、M1和P1基因多态与反流性食管炎易感性的关系。方法　采用病例 对照分子流行病学研究方法 ,以多重PCR技术检测GSTT1和GSTM 1基因缺失 ,以PCR RFLP技术检测GSTP1基因单核苷酸多态 (第 10 4密码子A→G)。结果　共检测了 10 9例反流性食管炎患者、97例有胃食管反流症状但胃镜检查阴性 (NERD)的患者和 97例正常对照者。GSTT1和GSTM 1基因缺失频率在食管炎组、NERD组和正常组分别为 48.6 %、42 .6 %、5 3 .6 %和 5 2 .0 %、5 3 .6 %、43 .3% ,差异无显著性。然而 ,反流性食管炎组突变型GSTP1(40 .4% )基因频率显著高于NERD组 (2 4.7% ,P <0 .0 5 )和正常对照组 (2 1.6 % ,P <0 .0 5 )。携带GSTP1变异基因型者比携带野生型基因型者发生反流性食管炎的风险高 2 .42倍 (95 %CI ,1.2 2～ 4.80 )。在携带GSTP1变异基因型同时无幽门螺杆菌感染的个体 ,食管炎的OR值则增加到 2 .6 7(95 %CI 1.0 6～ 6 .70 )。结论　GSTP1基因 (10 4密码子A→G)多态可能是涉及反流性食管炎发生的遗传易感因素。幽门螺杆菌感染可能会降低反流性食管炎的发生 ,它可能是反流性食管炎的保护因素。     

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。     

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。     

谷胱甘肽转硫酶T1基因型与溃疡性结肠炎易感性的关系

目的:探讨谷胱甘肽转硫酶(GST)T1基因型与中国浙江汉族人群溃疡性结肠炎(UC)易感性的关系.方法:应用聚合酶链反应技术检测99例溃疡性结肠炎(UC)患者和140例健康对照中的GSTT1基因型,采用χ2检验,分析比较GSTT1基因型在UC患者和健康人群中的分布差异.结果:GSTT1(-)基因型频率在UC组和对照组分布有显著性差异(64.7% vs 47.1%,P=0.007,OR=2.050,95%CI:1.208-3.480);根据UC临床特征进一步分层分析,GSTT1(-)基因型在远端UC中的分布频率高于广泛结肠UC(71.8%vs 31.3%,P=0.002);GSTT1(-)基因型与UC病情严重程度无关(P＞0.05).结论:GSTT1基因型与中国浙江汉族人群UC相关.     

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。     

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。     

Polymorphisms at GSTM1 and GSTT1 gene loci and susceptibility to cervical cancer in Indian population

Multiple allelism at loci encoding detoxifying enzymes is associated with cancer risk. Glutathione S-transferase (GSTs) catalyzes the conjugation of glutathione to numerous potentially genotoxic compounds. This study evaluates the influence of genetic polymorphisms of GST M1 and GST T1 on susceptibility to cervical cancer. A multiplex polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from cases with cervical cancer (n=142) and normal controls (n=96). The results showed that the frequency of homozygous GSTM1 null genotype was higher in cervical cancer cases (57.0%) as compared to controls (34.4%) and the differences were significant (p<0.05), OR=2.5, 95% CI: 1.4--4.5. The frequency of homozygous GSTT1 null genotype in cancer cases was 19.7% in comparison to 12.5% in controls, however, the difference was not statistically significant (OR=1.7, 95% CI: 0.8-3.8). Significant difference was found between the cases and controls in the distribution of the null genotype of GST M1 in individuals aged above 45 years (p=0.04), but this difference was not significant in individuals aged below 45 years (p=0.06). No significant differences were found in cervical cancer cases and controls when data were analyzed according to age group for GSTT1 null genotype. Further, the combined analysis of both GSTM1 null and GSTT1 null genotypes did not appear to influence the susceptibility to cervical cancer, suggesting that polymorphisms of other detoxifying enzymes may play a significant role in cervical carcinogenesis.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

OBJECTIVE: The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. MATERIAL AND METHODS: GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. RESULTS: The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03-2.71, p =0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89-9.97, p =0.0003). CONCLUSIONS: The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

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.     

Association of the glutathione S-transferase M1 homozygous null genotype with susceptibility to Sjögren's syndrome in Japanese individuals

OBJECTIVE: To investigate the role of polymorphisms of the glutathione S-transferase M1 (GSTM1) and GSTT1 genes in determining susceptibility to Sj?gren's syndrome (SS) and autoantibody production. METHODS: Polymorphisms of the GSTM1 and GSTT1 genes in 106 Japanese patients with primary SS and in 143 healthy controls were analyzed by polymerase chain reaction. RESULTS: Frequency of the GSTM1 homozygous null genotype was significantly increased in SS patients compared with controls (57.5% versus 44.1%; P = 0.035). Moreover, a significantly greater frequency of SSA antibodies was found among SS patients with the GSTM1 null genotype than among those with the GSTM1 non-null genotype (P = 0.0013). Frequency of the GSTT1 polymorphism was not different between SS patients and controls. CONCLUSION: The GSTM1 homozygous null genotype could be a genetic factor that determines susceptibility to SS and may be involved in SSA antibody production.     

Increased prevalence of GSTM(1) null genotype in patients with myelodysplastic syndrome: a case-control study

BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are clonal disorders of bone marrow stem cells characterized by ineffective hematopoiesis leading to blood cytopenia; they often progress to acute myeloid leukemia (AML). The glutathione S-transferases (GST) detoxify various agents, including those implicated in MDS. Both GSTM(1) and GSTT(1) genes have "null" alleles and are polymorphic. We studied the impact of GTM(1) and GSTT(1) null genotypes on the MDS susceptibility, disease severity and laboratory indices with prognostic value for the syndrome. MATERIAL AND METHODS: In a hospital-based case-control study we analyzed lymphocyte DNA samples from 54 patients with MDS and 60 cancer-free controls matched for age, sex, smoking habits and origin. A multiplex polymerase chain reaction was used to genotype both GSTM(1) and GSTT(1) simultaneously. The chi(2) test was used for statistical evaluation of the data and the odds ratios and attributable risk and population attributable risk were also calculated. RESULTS: A significantly increased frequency of GSTM(1) null genotype was found among MDS patients (57.4%) compared to controls (33.3%) (p < 0.01), while the frequency of GSTT(1) null genotype was not significantly higher in MDS patients (11.1% vs. 6.66%). Neither GSTM(1) and GSTT(1) null genotype was associated with a particular category of the French-American-British (FAB) classification in the patients studied. Additionally, GSTM(1) null genotype was associated with a significant decrease in the absolute number of neutrophils among the MDS patients. CONCLUSIONS: Individuals with GSTM(1) null genotype may have increased susceptibility to MDS. Null genotypes do not seem to have be associated with FAB classification while they may be associated with putative prognostic factors.     

Susceptibility to hepatocellular carcinoma associated with null genotypes of GSTM1 and GSTT1

ALM In order to study the association between the null genotypes of GSTM1 and GSTT1 and the genetic susceptibility to hepatocellular carcinoma (HCC). METHODS The genotypes of GSTM1 and GSTT1 of 63 cases of HCC and 88 controls were detected with the multiple PCR technique. RESULTS The frequency of GSTM1 null genotype was 57.1% among the cases, and 42.0% among the controls, the difference being statistically significant (x2 = 3.35, P = 0.067),but X2 value approaching the significance level.The odds ratio was 1.84 (95% Cl=0.91 - 3.37).The frequency of GSTT1 non-null genotype was 87.3% among the cases and 62.5% among the controls, the difference being statistically significant (X2=11.42, P=0.0007274). The odds ratio was 4.13 (95% Cl = 1.64 - 10.70).According to the cross analysis, the GSTT1 nonnull genotype was more closely associated with HCC than GSTM1 null genotype, and these two factors play an approximate addlitive interaction in the occurrence of HCC. CONCLUSION The persons with GSTM1 nullgenotype and GSTT1 non-null genotype have the increased risk to HCC.     

The link between genetic polymorphism of glutathione-S-transferases, GSTM1, and GSTT1 and diffuse large B-cell lymphoma in Egypt

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. A number of studies have examined the role of genetic polymorphisms in the risk of DLBCL, and several variants have been identified as potential susceptibility genes, of those glutathione-S-transferases T1 and M1 (GSTT1 and GSTM1).

Aim of the work

The aim of the current study was to investigate the influence of inherited genetic polymorphisms of GSTM1 and GSTT1 genes on the susceptibility to DLBCL in Egypt.

Methods

Genotyping of the candidate genes was performed for 71 Egyptian DLBCL patients and 100 age- and gender-matched healthy controls by multiplex polymerase chain reaction technique.

Results

The frequencies of GSTT1 null, GSTM1 null, and dual null genotypes among DLBCL patients were 47.9, 52.1, and 23.9?% respectively.

Conclusion

GSTT1 null genotype conferred almost fourfold increased risk of DLBCL (OR?=?3.9, 95?% CI?=?1.97–7.75), and the risk increased when confined to male patients (OR?=?4.4, 95?% CI?=?1.57–12.63), while GSTM1 null genotype was not associated with DLBCL risk. Further studies on the functional consequences of GSTT1 and GSTM1 genetic polymorphisms would pave the way to declare their role in the pathogenesis of DLBCL or as possible predictors for response to therapy.     

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.