Distribution of glutathione S-transferase M1, P1 and T1 genotypes in different age-groups of Finns without diagnosed cancer

BACKGROUND: Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of hazardous environmental agents, and their polymorphisms may therefore modify the risk of environmentally induced cancers. Consequently, the XME polymorphisms have been extensively studied in this context during recent years. Particular attention has been given to the polymorphisms of glutathione S-transferase (GST) M1, P1 and T1 genes. Previous studies have provided abundant data indicating these polymorphisms as important modifiers of individual susceptibility to cancers of environmental origin. It can be postulated that if the at-risk genotypes of these genes were real risk factors for the environmental cancers, their prevalence would presumably decrease with age in cancer-free part of the population. METHODS: We tested the hypothesis in a population based group of 2105 Finns (1,051 men, 1,054 women) in five age strata (27, 37, 47, 57 and 67 years of age), all without clinically diagnosed cancer. RESULTS: For GSTM1 genotype, a significant interaction was seen between gender and age among never smokers (p=0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31-1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97-2.97) homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the likelihood of being a concurrent carrier of the putatively protective genotypes of all of the three studied GSTs was almost three-fold (OR 2.80, 95% CI 1.10-7.12) in heavy smokers in the two oldest age-groups compared with the other genotypes. CONCLUSIONS: Our findings based on a novel study design provide support to the previous case-control studies suggesting that GST genotypes modify individual risk of environmentally-induced cancers.     

Glutathione S-transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women

Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n = 615) or fibrocystic breast conditions (n = 467) were compared to women without clinical breast disease (n = 878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105–Val allele (OR = 1.33, 95% CI, 0.99–1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR = 1.77, 95% CI, 1.03–3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105–Val allele needs confirmation in other studies.     

Glutathione S-transferase M1-null genotype as risk factor for SOS in oxaliplatin-treated patients with metastatic colorectal cancer

Background:

Oxaliplatin is used as a neo-adjuvant therapy in hepatic colorectal carcinoma metastasis. This treatment has significant side effects, as oxaliplatin is toxic to the sinusoidal endothelial cells and can induce sinusoidal obstruction syndrome (SOS), which is related to decreased overall survival. Glutathione has an important role in the defence system, catalysed by glutathione S-transferase (GST), including two non-enzyme producing polymorphisms (GSTM1-null and GSTT1-null). We hypothesise that patients with a non-enzyme producing polymorphism have a higher risk of developing toxic injury owing to oxaliplatin.

Methods:

In the nontumour-bearing liver, the presence of SOS was studied histopathologically. The genotype was determined by a semi-nested PCR.

Results:

Thirty-two of the 55 (58%) patients showed SOS lesions, consisting of 27% mild, 22% moderate and 9% severe lesions. The GSTM1-null genotype was present in 25 of the 55 (46%). Multivariate analysis showed that the GSTM1-null genotype significantly correlated with the presence of (moderate–severe) SOS (P=0.026).

Conclusion:

The GSTM1-null genotype is an independent risk factor for SOS. This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.     

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 of p53 polymorphisms and colorectal cancer: Modulation of risk and progression

Objectives

p53 Gene variants BstUI RFLP at codon 72 in exon 4, 16 bp tandem repeat in intron 3 and MspI RFLP in intron 6, which code for two functionally different protein isoforms, have been shown to modulate susceptibility to different types of human neoplasms.

Methods

p53 genotype was assessed in 90 CRC patients, 321 age-matched controls and 322 centenarians.

Results

The p53 codon 72 arginine, the p53 16 bp deletion, and the MspI RFLP were significantly more frequent in CRC patients in comparison to the controls and to the centenarians (odd ratio 1.44 and 1.93). In the CRC group, the BstUI RFLP polymorphism was the more frequent combination (62.2%), and it was significantly associated with highly infiltrating (p < 0.01), poorly differentiated (p < 0.01), and metastatic (p < 0.05) tumours.Our findings indicate that the p53 codon 72 polymorphisms are associated with a higher risk of CRC and are associated with more advanced and undifferentiated tumours.     

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。     

谷胱甘肽硫转移酶A1(GSTA1)基因多态性与前列腺癌和膀胱癌易感性的Meta分析

目的 探讨谷胱甘肽硫转移酶A1(GSTA1)基因多态性与前列腺癌及膀胱癌易感性的关系.方法 通过检索PubMed等数据库,获取GSTA1基因多态性与前列腺癌或膀胱癌的文献9篇,对1989例病例和2246例对照进行meta分析,以比值比(OR)和95%可信区间(CI)作为效应指标.结果 各遗传模型的Meta分析显示:GSTA1基因多态性与前列腺癌易感性的相关性无统计学意义[(AA vs BB:OR=0.92,95%CI:0.68~1.23,P=0.56);(AB vs BB:OR=1.02,95%CI:0.86~1.21,P=0.83);(AA/AB vs BB OR=1.01,95%CI:0.86~1.17,P=0.93);(AA vs AB/BB:OR=0.91,95%CI:0.69~1.20,P=0.51)].各遗传模型的Meta分析显示:GSTA1基因多态性与膀胱癌易感性的相关性无统计学意义[(AA vs BB:OR=0.97,95%CI:0.71~1.33,P=0.85);(AB vs BB:OR=1.11,95%CI:0.93~1.31,P=0.25);(AA/AB vs BB OR=1.07,95%CI:0.92~1.25,P=0.37);(AA vs AB/BB:OR=0.87,95%CI:0.64~1.18,P=0.37)].结论 单独的GSTA1基因多态性不是前列腺癌和膀胱癌的易感因素.     

Adiponectin gene and risk of colorectal cancer

Background:

Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.

Methods:

The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-wide association study in the ADIPOQ gene. Genotyping was also performed for a previously reported risk variant, rs266729, in 1062 individuals with a diagnosis of colorectal cancer and 1062 controls matched on age, gender and ethnicity (Jewish or not Jewish) as part of a population-based case–control study in Israel.

Results:

No evidence was found for an association between ADIPOQ and risk of colorectal cancer. The single nucleotide variant previously associated with decreased risk of colorectal cancer, rs266729, revealed an adjusted odds ratio of 1.04; 95% confidence interval, 0.88–1.23.

Conclusion:

The SNP, rs266729, was not strongly associated with colorectal cancer in patients of Ashkenazi Jewish descent or other ethnic groups in Israel.     

Reproductive factors,glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk

We conducted a hospital-based case–control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

Genetic alterations in chromosome 10q24.3 and glutathione S-transferase omega 2 gene polymorphism in ovarian cancer

The molecular basis of ovarian cancer development has not been fully elucidated. In this study, genetic alterations in ovarian cancer were identified by arbitrarily primed polymerase chain reaction (AP-PCR). A gene in DNA fingerprinting, amplified from primer AE11, was cloned, sequenced, and identified by comparison with known genes in the genome database. Gene amplification in chromosome 10q24.3 was identified and measured by real-time PCR. Three out of 20 cases harbored this gene amplification. This amplified region was identified as IVS-4 of the glutathione-S-transferase Omega 2 (GSTO2) gene. Therefore, the mutations in all 6 exons of the GSTO2 gene were determined. The A to G transition at codon 142 in exon 4 (AAT to GAT, N142D) was observed. The frequency of GSTO2 gene polymorphism was analyzed in 20 ovarian cancers, compared with 41 normal individuals. The gene frequencies of D142 and N142 allele in ovarian cancer cases were 0.3 and 0.7, whereas in normal females, they were 0.2 and 0.8, respectively. The odds ratio of D142 allele in ovarian cancer was 1.73 (95% CI = 0.51-5.89), indicating that this GSTO2 gene polymorphism may be associated with the risk of ovarian cancer.     

上海地区白血病谷胱甘肽S-转移酶T1和M1基因多态性分析

目的 研究谷胱甘肽S-转移酶(GSTs)T1、M1基因多态形态在上海地区白血病患者中的频率分布特征,探讨不同基因多态形态与白血病易感性之间的联系。方法 采用等位基因特异聚合酶链反应(AS-PCR)方法对上海地区61名白血病患者进行GSTF1、M1基因型分析,比较不同基因型在白血病组和同一地区正常人群组之间的分布频率差异,并就疾病类型、年龄和性别进行分层比较。结果 白血病组和正常对照组之间,GSTT10／0基因型以及GSTT10／0-GSTM10／0联合基因型的分布频率差异有显著性,缺损基因型在白血病组显著升高。进行疾病类型、性别以及年龄分层后,这种趋势在男性和低年龄(≤30岁)急性淋巴细胞白血病患者中依然存在。结论 GSTF10／0基因型和GSTT10／0-GSTM10／0联合基因型可能是罹患白血病的风险因子。     

Association of death receptor 4, Caspase 3 and 5 gene polymorphism with increased risk to bladder cancer in North Indians

Purpose

Perturbed apoptosis due to missense alterations in candidate tumor suppressor gene Death receptor 4 (DR4) and in caspases (Casp) lead to deregulated cell proliferation and cancer predisposition. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. To test our proposal we examined whether six single nucleotide polymorphisms (SNPs) of the DR4 and Casp3, 5 genes contrive the risk of bladder cancer (BC) in a North Indian population.

Materials and methods

Genotyping was performed in 200 BC patients and 225 controls by Allele-specific PCR and by polymerase chain reaction-restriction fragment length polymorphism.

Results

In DR4 Arg141His, BC patients having AA genotype (p = 0.036; OR = 2.51. In Casp5Leu13Phe G > C, significant association was observed with GC (p = 0.025; OR = 1.78) and also in GC + CC (p = 0.026; OR = 1.68). C allele carriers in Casp5Ala90Thr T > C showed low risk of BC (p = 0.036; OR = 0.83). While in Casp3 G > A, AG (p = 0.003; OR = 2.11), GG (p = 0.050; OR = 2.18), G allele (p < 0.001; OR = 1.85) and its carrier AG + GG (p = 0.001; OR = 2.12) have shown significant BC risk. Significant association between DR4 Ala228Glu polymorphism and smoking was observed in BC risk. Haplotype analysis demonstrated that DR4 (Thr209Arg-Arg141His-Ala228Glu) C-G-C is associated with 1.8 folds (OR = 1.85; p = 0.033) risk. GG genotype of Casp3 G > A polymorphism showed increased risk of recurrence (p = 0.009; HR = 5.20).

Conclusion

This study provided new support for the association of DR4 and Casp3, 5 in BC development, the tumorigenic effect of which was observed to be more enhanced in case of smoking exposure.     

Glutathione-S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in BRCA1/2 mutation carriers

Variation in penetrance estimates for BRCA1/2 carriers suggests that other environmental and genetic factors may modify cancer risk in carriers. The GSTM1, T1 and P1 isoenzymes are involved in metabolism of environmental carcinogens. The GSTM1 and GSTT1 gene is absent in a substantial proportion of the population. In GSTP1, a single-nucleotide polymorphism that translates to Ile112Val was associated with lower activity. We studied the effect of these polymorphisms on breast cancer (BC) risk in BRCA1/2 carriers. A population of 320 BRCA1/2 carriers were genotyped; of them 262 were carriers of one of the three Ashkenazi founder mutations. Two hundred and eleven were affected with BC (20 also with ovarian cancer (OC)) and 109 were unaffected with BC (39 of them had OC). Risk analyses were conducted using Cox proportional hazard models adjusted for origin (Ashkenazi vs non-Ashkenazi). We found an estimated BC HR of 0.89 (95% CI 0.65-1.12, P=0.25) and 1.11 (95% CI 0.81-1.52, P=0.53) for the null alleles of GSTM1 and GSTT1, respectively. For GSTP1, HR for BC was 1.36 (95% CI 1.02-1.81, P=0.04) for individuals with Ile/Val, and 2.00 (95% CI 1.18-3.38) for carriers of the Val/Val genotype (P=0.01). An HR of 3.20 (95% CI 1.26-8.09, P=0.01), and younger age at BC onset (P=0.2), were found among Val/Val, BRCA2 carriers, but not among BRCA1 carriers. In conclusion, our results indicate significantly elevated risk for BC in carriers of BRCA2 mutations with GSTP1-Val allele with dosage effect, as implicated by higher risk in homozygous Val carriers. The GSTM1- and GSTT1-null allele did not seem to have a major effect.     

ERCC6/CSB gene polymorphisms and lung cancer risk

Nucleotide excision repair (NER) enzymes are critical for the removal of bulky DNA adducts caused by environmental carcinogens such as smoking. Of them, Cockayne syndrome complementation group B (CSB), coded by ERCC6, recruits NER repair factors to the DNA damage site and plays an important role in the repair process. Genetic variants of ERCC6 may alter the regulation of DNA repair and therefore were hypothesized to be associated with altered risk of smoking-related lung cancer. To test this hypothesis, we genotyped eight tagging single nucleotide polymorphisms (tSNPs) and three potentially functional SNPs of ERCC6 in 500 incident lung cancer cases and 517 controls in a Chinese population. Single locus analyses showed that none of the single SNP alone had the significant main affect on the risk of lung cancer. However, the combined variant genotypes of the four loci with P(trend) approaching to 0.10 (rs2228526, rs4253160, rs12571445 and rs3793784) were associated with a significantly increased lung cancer risk (adjusted OR 1.35, 95% CI, 1.04-1.75 among subjects carrying three or more variant alleles), indicating that multiple loci in ERCC6 may jointly contribute to the susceptibility of lung cancer. These findings, if validated, may contribute to identify at-risk subjects in the general population for smoking-related lung cancer.     

Polymorphism of cytosolic serine hydroxymethyltransferase,estrogen and breast cancer risk among Chinese women in Taiwan

Cytosolic serine hydroxymethyltransferase (cSHMT) is key to intersection of folate-metabolic pathway, participating in the pyrimidine synthesis for DNA repair. Based on the hypothesis that variants of the cSHMT C1420T together with methionine synthase (MS A2756G) and 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) are associated with breast cancer, we performed a multigenic case-control study of the effects to breast cancer risk of four polymorphisms of folate-metabolizing genes against duration of estrogen exposure. Support of our hypothesis came from the following observations: (i) Allelic frequency of cSHMT C1420T was higher in the controls than in the cases, manifesting a 0.56-fold risk reduction in breast cancer (95%CI = 0.39-0.80); and this association was more significant in those women are susceptible to time of estrogen exposure. (ii) A joint effect of the cSHMT and MS polymorphisms significantly reduced susceptibility to breast cancer (aOR = 0.55; 95%CI = 0.34-0.88). (iii) There was a trend toward a reduced risk of breast cancer in women carrying a greater number of putative low-risk genotypes (Ptrend = 0.048). (iv) This synergistic effects on risk reduction was significantly interacted with length of estrogen exposure, exhibiting a longer time of estrogen exposure (> or =30 years), menarche-to-FFTP interval (>11 years), age at the first full-term pregnancy (< or =25 years), and body mass index (< or =24). In conclusion, our study provides support to account for the preferential role of cSHMT polymorphism to lower risk of female breast cancer, and such reduced risk would be more significant in carriers with the polymorphisms of MS and MTHFR genes.     

A population-based study of glutathione S-transferase M1, T1 and P1 genotypes and risk for lung cancer

A deletion polymorphism for glutathione S-transferase M1 (GSTM1) has been related to risk for lung cancer among smokers in some studies but not in others. We examined GSTM1, a GSTT1 deletion polymorphism and a common GSTP1 gene variant (iso→val), as risk factors for lung cancer in a population-based case-control study of men. Cases (N=274) were males identified from 1993 to 1996 through the Fred Hutchinson Cancer Research Center Cancer Surveillance System registry for western Washington State. Male age-matched controls (N=501) were selected by random-digit dialing. Subjects participated in a telephone interview and blood draw. GSTM1 and GSTT1 were genotyped with a multiplex PCR assay using beta-globin as a positive control, and GSTP1 single nucleotide variant determined with PCR-based oligonucleotide ligation assays. GSTM1 absence was associated with a modest elevation in risk among all cases (odds RATIO=1.27, 95% CI 0.91–1.77) and among non-small cell cancers (adenocarcinoma OR=1.58, 95% CI 0.99–2.52; squamous cell OR=1.40, 95% CI 0.83–2.34). Risk associated with GSTM1 null was increased two to sixfold among heavy smokers. GSTT1 was not associated with lung cancer risk and GSTP1 val was non-significantly associated with a modest reduction in risk, particularly among heavy smokers. No specific combination of GST genotypes was particularly associated with risk. These results support previous reports that the GSTM1 null genotype is associated with a modest increase in risk for lung cancer, particularly among heavy smokers, suggest no role for GSTT1 and the need for further study of GSTP1.     

Glutathione S-transferase M1 and T1 polymorphisms: Susceptibility and outcomes in muscle invasive bladder cancer patients

BackgroundWe investigated whether genetic polymorphisms in the glutathione S transferase mu (GSTM1) and theta (GSTT1) genes modulated risk, disease progression and survival in primary muscle invasive bladder cancer (MIBC).MethodsGSTM1 and GSTT1 polymorphisms were analysed by multiplex polymerase chain reaction (PCR) using blood genomic DNA in 110 MIBC patients and 220 gender- and age-matched healthy controls. The influence of the genetic polymorphisms on patient survival was evaluated by Kaplan–Meier survival curves and Cox Proportional Hazard models. We also evaluated whether cigarette smoking and treatment modality modified the association between genotype and prognosis.ResultsGSTM1-null individuals exhibited increased risk for MIBC and an association with cigarette smoking. GSTT1-null subjects showed significant disease progression and cancer-specific death. In the combined analysis, GSTT1-null genotype was an independent risk factor for disease progression and cancer specific death regardless of GSTM1 genotype. Significant differences in progression-free survival (PFS) and cancer-specific survival (CSS) were seen based on GSTT1 genotype. The survival impact of the GSTT1 genotype was only valid for smokers. The GSTT1-null genotype was an independent prognostic factor for shorter PFS in patients who received chemotherapy and those who did not undergo radical cystectomy. By multivariate Cox regression analysis, GSTT1-null genotype was a predictive factor for disease progression and cancer specific survival regardless of treatment modality.ConclusionsThe GSTM1-null genotype plays an important role in genetic susceptibility to MIBC and the GSTT1-null genotype is associated with disease progression and shorter survival in MIBC.     

食管癌患者放疗前后血中pi类谷胱甘肽S－转移酶水平的测定

用放射免疫法（ＲＩＡ）检测了４０例正常人及６６例食管癌患者放疗前后血浆Ｐｉ类谷胱甘肽Ｓ－转移酶（ＧＳＴ－π）水平。结果显示：食管癌患者放疗前血浆ＧＳＴ－π水平显著高于正常对照（Ｐ＜０．００１），且水平和食管病变长度呈正相关。放疗后血浆ＧＳＴ－π水平显著降低（Ｐ＜０．０１），其水平在完全缓解（ＣＲ）病例与正常对照无明显差异（Ｐ＞０．０５），在部分缓解（ＰＲ）病例仍高于正常对照（Ｐ＜０．００１）。说明食管癌患者血浆ＧＳＴ－π水平与其肿瘤的消长密切相关，有可能成为疗效和判断预后的一个监测指标。