Multiplex PCR with Confronting Two-pair Primers for CYP1A1 Ile462Val,GSTM1, GSTT1, and NQO1 C609T

Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) is an effective genotyping method ‍for single nucleotide polymorphisms (SNPs) in aspects of reducing time and costs for analysis. So far we have ‍established PCR-CTPP conditions for tens of SNPs, including a triplex genotyping (Kawase et al., 2003). In the ‍present study we report a quadruplex PCR-CTPP to genotype simultaneously four functional polymorphisms of ‍carcinogen-metabolizing enzymes, CYP1A1 Ile462Val, GSTM1 null, GSTT1 null and NQO1 C609T, which were ‍reported that they have significant associations with smoking-related cancers. We applied this method for 475 health ‍check-up examinees to demonstrate the performance. Among the subjects, the genotype frequency of CYP1A1 ‍Ile462Val was 56.8% for Ile/Ile, 38.1% for Ile/Val and 5.1% for Val/Val. The null type frequencies of GSTM1 and ‍GSTT1 were 52.8% and 49.9%, respectively. And the genotype frequency of NQO1 C609T was 41.9% for C/C, ‍41.3% for C/T and 16.8% for T/T. Their distributions were similar to those reported for Japanese by other studies. ‍To the best of our awareness, this is the first paper that reports the success in quadruplex PCR-CTPP. The applied ‍polymorphisms are useful ones, which would be adopted not only for research purposes, but also for risk assessment ‍of individuals exposed to carcinogenic substances. This convenient genotyping would be applied for cancer prevention ‍especially in Asian Pacific regions, where expensive genotyping methods are hardly available.     

GSTT1 and GSTM1 Deletions,NQO1 C609T Polymorphism and Risk of Chronic Myelogenous Leukemia in Japanese

We conducted a prevalent case-control study with 51 chronic myelogenous leukemia (CML) cases and 476 controls ‍to investigate the associations between glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1 (GSTM1) ‍deletions, and the NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism with risk of chronic myelocytic ‍leukemia in Japanese. For the GSTT1 deletion, when the GSTT1 positive genotype was defined as the reference, the ‍OR for the GSTT1 deletion genotype was 1.32 (95%CI; 0.74-2.36). For the GSTM1 deletion, when the GSTM1 ‍positive genotype was defined as the reference, the OR for the GSTM1 deletion genotype was 0.95 (95%CI; 0.53- ‍1.69). For NQO1 C609T polymorphism, when the NQO1 609CC genotype was defined as the reference, the ORs for ‍the CT genotype, TT genotype, and CT and TT genotypes combined together were 2.37 (95%CI, 1.21-4.67, P=0.012), ‍1.44 (0.55-3.74, P=0.012) and 2.12 (1.10-4.08, P=0.025), respectively. The present study revealed that the risk of CML ‍was modulated little by GSTT1 and GSTM1 deletions, but a statistically significant association between NQO1 C609T ‍polymorphism and CML was observed for Japanese. Incidence case-control studies with a larger statistical power ‍are now required to confirm our findings.     

谷胱甘肽硫转移酶M1与T1基因缺失增加鼻咽癌易感性(英文)

目的在中国西南的广西壮族自治区的鼻咽癌高发区内研究谷胱甘肽硫转移酶 M1与 T1遗传多态性与鼻咽癌易感的相关性。方法病例与对照研究这些酶的遗传多态性(GSTM1和 GSTT1零基因型),鼻咽癌总数为127例,对照207例。结果 GSTM1和 GSqT1零基因型的频数在 NPC 患者中较高,差异达统计学意义(P<0.001)。结论鼻咽癌是广西最常见癌症,GST 酶与多种环境致癌物的解毒相关,同合子缺失 GSTM1和 GSTT1与数种癌相关,生鼻咽癌危险性已知与环境因素如吸烟和 EB病毒感染相关联,我们的结果提示 GSTM1和 GSTF1缺失多态性与增加鼻咽癌易感性相关,若两种解毒酶基因同时缺失对鼻咽癌易感受性意义更重要。     

谷胱甘肽硫转移酶M1与Tl基因缺失增加鼻咽癌易感性

目的在中国西南的广西壮族自治区的鼻咽癌高发区内研究谷胱甘肽硫转移酶M1与T1遗传多态性与鼻咽癌易感的相关性。方法病例与对照研究这些酶的遗传多态性(GSTM1和GSTT1零基因型),鼻咽癌总数为127例,对照207例。结果GSTM1和GSTT1零基因型的频数在NPC患者中较高,差异达统计学意义(P<0.001)。结论鼻咽癌是广西最常见癌症,GST酶与多种环境致癌物的解毒相关,同合子缺失GSTM1和GSTT1与数种癌相关,生鼻咽癌危险性已知与环境因素如吸烟和EB病毒感染相关联,我们的结果提示GSTM1和GSTT1缺失多态性与增加鼻咽癌易感性相关,若两种解毒酶基因同时缺失对鼻咽癌易感受性意义更重要。     

广西扶绥县肝癌高发家系谷胱甘肽转硫酶GSTM_1和GSTT_1基因多态性的研究

目的探讨广西扶绥县肝癌高发区壮族人群谷胱甘肽转硫酶GSTM1和GSTT1的基因多态性在肝癌家族聚集性中的作用,以及一级亲属与先证者之间HCC易感性的关系。方法采用病例-对照研究方法,收集21个广西扶绥县壮族肝癌家系76例,以及该地区21个对照家系68例,采用多重PCR技术和凝胶成像分析方法,对入选者GSTM1和GSTT1基因型进行检测,用ELISA法检测HBsAg,并将实验结果与临床资料相结合,进行统计学分析。结果①GSTM1基因空白型在肝癌家系组、对照家系组之间的频率分别为67.1%和36.8%(P=0.000);GSTT1基因空白型在肝癌家系组、对照家系组之间的频率分别为40.8%和19.1%(P=0.005);GSTM1和GSTT1基因同时缺失在肝癌家系组、对照家系组的频率分别为31.6%和2.9%(P=0.000)。②将GSTM1及GSTT1基因同时表达型为基准计算两基因联合作用的危险度,GSTM1基因缺失GSTT1基因表达型、GSTM1基因表达GSTT1基因缺失型、GSTM1基因及GSTT1基因联合缺失型的OR值分别为0.102、0.210和3.092。③GSTM1基因空白型在先证者与其直系亲属之间的频率分别为71.4%和65.5%(P=0.620),GSTT1基因空白型在先证者与其直系亲属之间的频率分别为47.6%和38.2%(P=0.454)。GSTM1和GSTT1基因同时缺失在先证者与其直系亲属之间的频率分别为33.3%和30.9%(P=0.839),差异均无统计学意义(P>0.05)。结论①GSTM1和GSTT1基因的多态性与肝癌家族聚集性相关;②GSTM1和GSTT1基因联合缺失与HCC的发生呈显著正相关,且两基因可能具有协同作用;③直系亲属与先证者HCC发生率无差别。     

广西扶绥县肝癌高发家系谷胱甘肽转硫酶GSTM1和GSTT1基因多态性的研究

目的探讨广西扶绥县肝癌高发区壮族人群谷胱甘肽转硫酶GSTM1和GSTT1的基因多态性在肝癌家族聚集性中的作用,以及一级亲属与先证者之间HCC易感性的关系。方法采用病例一对照研究方法,收集21个广西扶绥县壮族肝癌家系76例,以及该地区21个对照家系68例,采用多重PCR技术和凝胶成像分析方法,对入选者GSTM1和GSTT1基因型进行检测,用ELISA法检测HBsAg,并将实验结果与临床资料相结合,进行统计学分析。结果（1）GSTM1基因空白型在肝癌家系组、对照家系组之间的频率分别为67．1％和36．8％（P=0．000）;GSTT1基因空白型在肝癌家系组、对照家系组之间的频率分别为40．8％和19．1％（P=-0．005）;GSTM1和GSTT1基因同时缺失在肝癌家系组、对照家系组的频率分别为31．6％和2．9％（P=0．000）。②将GSTM1及GSTT1基因同时表达型为基准计算两基因联合作用的危险度,GSTM1基因缺失GSTT1基因表达型、GSTM1基因表达GSTT1基因缺失型、GSTM1基因及GSTT1基因联合缺失型的OR值分别为0．102、0．210和3．092。（3）GSTM1基因空白型在先证者与其直系亲属之间的频率分别为71．4％和65．5％（P=0．620）,GSTT1基因空白型在先证者与其直系亲属之间的频率分别为47．6％和38．2％（P=0．454）。GSTM1和GSTT1基因同时缺失在先证者与其直系亲属之间的频率分别为33．3％和30．9％（P=-0．839）,差异均无统计学意义（P〉0．05）。结论（1）GSTM1和GSTT1基因的多态性与肝癌家族聚集性相关;（2）GSTM1和GSTT1基因联合缺失与HCC的发生呈显著正相关,且两基因可能具有协同作用;③直系亲属与先证者HCC发生率无差别。     

Association between Helicobacter pylori seropositivity and NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism observed in outpatients and health checkup examinees

Background Significant associations of Helicobacter pylori (H. pylori) seropositivity have been found with several host polymorphisms. This study investigated the associations of functional polymorphisms of the NQO1, GSTM1, and GSTT1 genes of detoxification enzymes, with the seropositivity, as well as with pepsinogen levels, as markers of gastric atrophy.Methods The subjects were 241 noncancer outpatients who had participated in an H. pylori eradication program (HPE) at Aichi Cancer Center Hospital, and 465 health checkup examinees in Nagoya (HCE). The NQO1 C609T, GSTM1, and GSTT1 polymorphisms were determined by triplex polymerase chain reaction with confronting two-pair primers (PCR-CTPP).Results The sex- and age-group-adjusted odds ratio (OR) of NQO1 C/C for H. pylori seropositivity relative to T/T was highly significant; OR, 1.92; 95% confidence interval (95% CI), 1.22–3.03. The ORs of the GSTM1 present type and GSTT1 present type for H. pylori seropositivity were not significant; OR, 0.87; 95% CI, 0.64–1.20 and OR, 1.14; 95% CI, 0.83–1.57, respectively. The association of the NQO1 C/C genotype with H. pylori seropositivity was observed only for never-smokers; OR, 2.25; 95% CI, 1.33–3.79. The genotypes of the NQO1, GSTM1, and GSTT1 genes were not associated with the development of atrophic gastritis among the H. pylori-seropositive subjects.Conclusion This is the first study to report a significant association of the NQO1 C609T polymorphism with H. pylori seropositivity. The biological mechanism explaining the significant association with the seropositivity remains to be elucidated.     

谷胱甘肽转移酶T1和M1基因多态性及吸烟与结直肠癌关系的对照研究

目的　研究谷胱甘肽转移酶 (GSTs)M1、T1基因多态性与结直肠癌易感性的关系。方法12 6例结直肠癌患者和 343例随机抽样的正常对照者 ,应用多重聚合酶链反应 (PCR)方法检测其GSTM1和GSTT1基因多态性 ,采用非条件Logistic回归模型分析基因型、吸烟情况与结直肠癌患病的关系。结果　GSTM1和GSTT1缺陷型基因型在对照人群中的频率分布为 5 5 .5 %和 2 0 .4 %。在GSTT1缺陷型基因型的人群中 ,GSTM1缺陷型患直肠癌风险是非缺陷型者的 9.74倍 (95 %CI为 1.13～83.85 )。现在吸烟者中 ,GSTM1缺陷型基因型患结肠癌的风险是非缺陷型者的 2 .2 2倍 (P >0 .0 5 ) ;GSTT1缺陷型基因型患结肠癌的风险是非缺陷型者的 4 .5 5倍 (95 %CI为 1.14～ 18.17) ,患直肠癌的风险是非缺陷型者的 4 .6 0倍 (95 %CI为 1.11～ 19.11)。结论　GSTM1和GSTT1缺陷型基因型有可能增加结直肠癌的危险性 ,其危险性主要表现在两者的联合作用上 ;环境暴露因素———吸烟和相关代谢酶多态性也表现出增加结直肠癌危险性的联合作用。     

Allelic Variation of GSTT1, GSTM1 and GSTP1 Genes in a North Indian Population

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic ‍compounds. Homozygous deletions or null genotypes of GSTT1 and GSTM1 genes and an A to G substitution at ‍nucleotide 313 in GSTP1 have been reported in different populations. Intra-ethnic as well as interethnic differences ‍are known to exist in the frequencies of the above GST genes. The present study was therefore undertaken to ‍determine the prevalence of GSTM1 and GSTT1null alleles, as well as the GSTP1 gene polymorphism, in 370 ‍healthy individuals in a North Indian population. Genotyping of M1 and T1 was performed using a multiplex ‍polymerase chain reaction and the GSTP1 polymorphism was determined by the polymerase chain reaction/restriction ‍fragment length polymorphism (PCR-RFLP) method. The frequencies of GSTM1 and GSTT1 null alleles in normal ‍healthy individuals were observed to be 33.0% and 18.4% respectively. In 7.0% of individuals’ concomitant lack of ‍M1 and T1 genes were observed. For GSTP1, wild (Ile/Ile), heterozygous (Ile/Val) and mutant (Val/Val) genotypes ‍were observed for 44.3%, 50.3% and 5.4% of individuals respectively. The prevalence of the M1 null allele is ‍significantly lower than those documented for English, Turkish, Chinese, Caucasians, Japanese and white (Brazilian ‍and American) populations. However, a significantly higher frequency for T1 null was reported in Chinese and ‍Japanese population. Furthermore, Japanese and African American populations have exhibited significantly higher ‍frequencies of wild and mutant P1 genotypes, respectively, than the Indian population. Thus, our results signify an ‍impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

Association of Glutathione-S-Transferases M1 and T1 Deletional Variants with Development of Oral Squamous Cell Carcinoma: A Study in the South-East of Iran

Background: The role of genetic polymorphisms in genes of Glutathione-S-transferases (GST) enzymes in susceptibilityto oral cavity cancers is controversial. Oral Squamous Cell Carcinoma (OSCC) is the most common oral cavity neoplasm.Aimed to evaluate the potential impacts of two well-known null variants residing in the gene encoding GSTM1 andGSTT1 enzymes of OSCC patients in the southeast of Iran. Methods: In a case-control design, 113 individuals (50OSCC patients, and 63 healthy subjects) were included. DNA was extracted using paraffin-embedded tissues. GSTgenotyping was carried out using multiplex PCR. Results: In 113 participants, 41 (36.3%) and 72 (63.7%) were malesand females respectively. No significant difference was recognized for distribution of GSTM1 (P=0.11) and GSTT1(P=0.28) null genotypes between OSCC patients (58%, and 24% respectively) and healthy controls (42.9% and 15.9%respectively). Also, no significant difference was noted regarding the frequency of GSTM1 null genotype in differenthistological grades, however, those patients with more aggressive disease (poorly differentiated or grade III) revealedwith a significantly higher ratio (66.7%) of GSTT1 null genotype (P=0.002). The highest odds ratio for OSCC was relatedto combined null genotypes for GSTM1 and GSTT1 (OR=2.5, 95% CI: 0.7-9.2), however, this was not statisticallysignificant finding (P=0.15). Conclusion: Null genotypes polymorphisms were more common in OSCC than healthyindividuals. GSTT1 null genotype may be an important genetic factor in the progression of OSCC.     

肝细胞癌、鼻咽癌患者谷胱甘肽硫转移酶M1和T1基因型分布

目的 探讨高危区肝细胞癌和鼻咽癌患者谷胱甘肽硫转移酶M1 (GSTM1) 及T1 (GSTT1)基因多态性的分布。方法 应用PCR技术检测181例肝细胞癌、126例鼻咽癌患者和641例对照组人体GSTM1和GSTT1基因型。结果 GSTM1空白基因型(null)在肝癌组、鼻咽癌组与对照组频率分别为65.2%、61.9%和47.6%,病例组与对照组比较,差异有统计学意义（P＜0.01)。GSTT1空白基因型(null)在肝癌组、鼻咽癌组与对照组频率分别为57.5%、62.7%和43.1%,病例组与对照组比较,差异有统计学意义（P＜0.001)。结论 在肝细胞癌、鼻咽癌高发区解毒酶基因GSTM1和GSTT1呈多态性分布,二者的null基因型均增加患肝细胞癌、鼻咽癌的风险。     

NQO1基因多态性与膀胱癌易感性的关系

[目的]探讨浙江地区依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶1(NQO1)基因多态性与膀胱癌易感性的关系.[方法]采用病例对照研究方法,应用相对的两对引物—聚合酶链反应技术(PCR-CTPP),对99例膀胱癌患者和100例非肿瘤患者的NQO1 C609T基因型进行检测,并分析其与膀胱癌易感性的关系.[结果]NQO1 C609T基因型分布频率在膀胱癌组和对照组之间的差异具有统计学意义(P＜0.05),携带609TT基因型的个体罹患膀胱癌的风险是携带609CC基因型个体的2.448倍(95％CI为1.125～5.326).NQO1 C609T基因型分布频率在膀胱癌不同病理分级和临床分期之间的差异均无统计学意义(P＞0.05).[结论]NQO1 C609T基因多态性可能与膀胱癌的易感性相关,携带NQO1 609TT基因型的人群易患膀胱癌.     

Polymorphisms in GSTM1, GSTTI and GSTP1 and nasopharyngeal cancer in the east of China: a case-control study

Aim: The study was performed to assess the potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in the risk of nasopharyngeal cancer in Chinese population. Method: We collected 182 cases undergoing pathologic examination and 366 controls from the affiliated hospital of Medical College of Qingdao University from April 2006 to July 2010. Genotyping was based upon duplex polymerase-chain-reactions with the PCR-CTPP method. Results: More smokers were found in NPC patients than controls, and a higher IgA/VCA+ . Individuals carrying null GSTM1 and GSTT1 had 1.76 and 2.01 fold risk of NPC when compared with non-null genotypes, respectively. A non-significant increase risk of NPC was found in individuals with 1b/1b genotype when compared with 1a/1a genotype (OR=1.32, 95%CI=0.60-2.94). When compared with non-null GSTM1 and GSTT1 genotypes, the combination of null/null GSTM1 and GSTT1 genotypes showed moderate increased risk of NPC (OR=3.03, 95% CI=1.74-5.08). Conclusion: Our study provides evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to NPC in Chinese population, while GSTP1 may not. Our findings provide information relevant to the prevention of NPC.     

Frequency and Association Of GSTM1 and GSTT1 Gene Polymorphisms with Survival in Breast Cancer Patients

Objective: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.     

Glutathione S-transferase gene polymorphisms and risk of gastric cancer in a Chinese population

Aim: The potential role of GSTM1, GSTT1 and GSTP1 polymorphisms in risk of gastric cancer in Chinese was studied. Methods: We collected 194 gastric cancers by pathologic examination and 412 controls from southern China during January 2007 to January 2011. Genotyping was based upon duplex polymerase-chain-reaction withthe PCR-CTPP method. Results: Individuals carrying null GSTM1 and GSTT1 had 1.49 and 1.96 fold risk sof gastric cancer when compared with respective non-null genotypes. We also found a non-significant 37% excess risk of gastric cancer among carriers of GSTP1 1b/1b genotype when compared with 1a/1a genotype (OR=1.37, 95% CI=0.81-2.25). The combination of null/null GSTM1 and GSTT1 genotypes showed higher increased risk of gastric cancer (OR=3.17, 95% CI=1.68-4.21). Moreover, cancers in ever smokers and ever drinkers were observed to be strongly associated with null GSTM1 and GSTT1, and a significant cancer risk was observed in positive H.pylori infection individuals with null GSTT1. Conclusion: Our study provided evidence that genetic deletion of GSTM1 and GSTT1 may contribute to increased susceptibility to gastric cancer in our Chinese population, while the GSTP1a/b polymorphism may not.     

Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility.

Lung adenocarcinoma has replaced squamous cell lung carcinoma as the most frequent histological subtype in lung cancers. However, genetic factors that affect cancer susceptibility are much less understood in adenocarcinoma than in squamous cell carcinoma. In this study, polymorphisms in five genes involved in the metabolism of carcinogens or in the repair of damaged DNA in lung cells, NQO1-Pro187Ser, GSTT1-positive/null, GSTM1-positive/null, CYP1A1-Ile462Val, and OGG1-Ser326Cys, were examined for association with lung adenocarcinoma risk in a case-control study of 198 patients and 152 control subjects. The NQO1 and GSTT1 polymorphisms were associated with lung adenocarcinoma risk with adjusted odds ratio of 2.15 for the NQO1-Pro/Pro genotype versus the Ser/Ser genotype and adjusted odds ratio of 1.61 for the GSTT1-null genotype versus the positive genotype, respectively. Furthermore, individuals with the combined genotype of NQO1-Pro/Pro and GSTT1-null showed greater risk compared with those of NQO1-Ser/Ser and GSTT1-positive. In contrast, significant association was not observed for the GSTM1, CYP1A1, and OGG1 polymorphisms with lung adenocarcinoma risk, although several studies have shown their implication in the risk for squamous cell lung carcinoma. The result indicates that the NQO1-Pro/Pro and GSTT1-null genotypes are risk factors for lung adenocarcinoma development, and that the genetic factors for susceptibility to adenocarcinoma are different from those to squamous cell carcinoma. The enhanced risk of the NQO1-Pro/Pro genotype combined with the GSTT1-null genotype was more evident in smokers than in nonsmokers. Therefore, carcinogens in tobacco smoke, which are activated by NQO1 and detoxified by GSTT1, could have a role in lung adenocarcinoma development.     

Polymorphism in GSTM1, GSTT1, and GSTP1 and Susceptibility to Lung Cancer in a Japanese Population

Polymorphisms in glutathione S-transferases (GSTs) may predispose to lung cancer through deficient detoxification ‍of carcinogenic or toxic constituents in cigarette smoke, although previous results have been conflicting. Three GST ‍polymorphisms (GSTM1, GSTT1 and GSTP1) were determined among 86 male patients with lung carcinomas and ‍88 healthy male subjects. We found no significant increase in the risk of lung cancer for any genotypes for the nulled ‍GSTM1 [odds ratio (OR)=2.0; 95% confidence interval (95% CI)= 0.8-5.3], the nulled GSTT1 (OR=2.0; 95% CI=0.8- ‍5.1) or the mutated (the presence of a Val-105 allele) GSTP1 (OR=0.96; 95% CI=0.4-5.5). The GST polymorphisms ‍alone may thus not be associated with susceptibility to lung carcinogenesis in male Japanese. However, individuals ‍with a concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR=2.7; 95% CI=1.0-7.4) when ‍compared with those having at least one of these genes. No other combinations were associated with lung cancer ‍risk. These results suggest that there may be carcinogenic intermediates in cigarette smoke that are substrates for ‍both GSTM1 and GSTT1 enzymes and that lung cancer risk is increased for individuals who are doubly deleted at ‍GSTM1 and GSTT1 gene loci. Additional large studies are needed to confirm this observation.     

Glutathione S-transferase T1 and M1 gene defects in ovarian carcinoma

Glutathione S-transferases (GSTs) M1 and T1 are known to be polymorphic in humans. Both polymorphisms are due to gene deletions, which are responsible for the existence of null genotypes. The gene defect of GSTT1 has been reported to be associated with an increased risk of myelodysplastic syndromes, astrocytoma and meningioma. A lack of GSTM1 was associated with tobacco smoke-induced lung and bladder cancer. In this study we examined whether the GSTT1 and/or GSTM1 homozygous null genotypes were associated with an increased risk of ovarian cancer using a multiplex polymerase chain reaction protocol. The GSTT1 null genotype was observed in 14% of the control subjects that had never suffered from neoplastic disease (n=115) and in 16% of the patients affected with ovarian cancer (n=103, OR 0.87, 95% CI 0.39–1.92, P=0.73). A lack of GSTM1 was observed in 38% of the control subjects and in 46% of the patients (OR 0.77, 95% CI 0.44–1.32). This difference was not significant (P=0.34). Similarly, no significant differences were obtained if GSTT1 and/or GSTM1 null genotypes were analyzed in subgroups of control subjects and ovarian cancer patients between the ages of 20–40, 41–70 and 71–90 years and in individuals with a positive family history of neoplastic disease. GSTT1 and/or GSTM1 null genotypes were not significantly associated with the histologic type and grade or FIGO (International Federation of Gynecology and Obstetrics) stages of the ovarian carcinomas. In conclusion, GSTT1 and/or GSTM1 null genotypes are not markers for an increased risk of ovarian cancer.     

中国南方粤语方言地区汉族人群GSTM1、GSTT1基因多态性

背景与目的:了解谷胱甘肽-S-转移酶M1、T1(GSTM1、GSTT1)基因多态性在中国南方粤语方言地区健康人群中的分布规律,初步探讨其与人群某些疾病家族史之间的关系。材料与方法:根据研究目的在广东省新兴县和广东省广州市两个地区选择符合条件的健康人群606人作为研究对象。应用聚合酶链式反应-2%琼脂糖凝胶电泳的方法检测调查对象GSTM1、GSTT1基因型。结果:在调查人群中,GSTM1基因纯合缺失基因型GSTM1(-/-)的出现频率为56.8%(n=597);GSTT1基因纯合缺失基因型GSTT1(-/-)的出现频率为42.1%(n=579);两基因联合缺失的频率为22.8%(n=570)。结论:GSTM1与GSTT1基因之间在人群中分布相互独立,无连锁现象,GSTM1基因在两个不同地区来源人群中的分布有显著差异。GSTT1在人群中不同基因型的分布与研究人群中冠心病疾病家族史的发生之间显著关联,有冠心病家族史人群GSTT1缺失基因型的表达显著增加。     

Glulathione-S-transferases Gene Polymorphism in Prediction of Gastric Cancer Risk by Smoking and Helicobacter Pylori Infection Status

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastriccancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched casecontrolstudy with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 andGSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantlyassociated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95%CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was foundfor GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes withthe risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk ofgastric cancer, and smoking modifies the association.