Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression

Choi, Suck Chei; Yun, Ki Jung; Kim, Tae Hyeon; Kim, Hyun Ju; Park, Seh Geun; Oh, Gyung Jae; Chae, Soo Cheon; Oh, Gyung-Jae; Nah, Yong Ho; Kim, Jeong Joong; Chung, Hun Tag

doi:10.1016/s0304-3835(03)00158-7

Cited by 44 publications

(27 citation statements)

References 38 publications

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“…21 Other studies, some of which were hospitalbased and mostly carried out in Asian populations, have shown that GST null genotypes did not contribute to an increased GC risk. 24,[27][28][29] Our analyses did not show any evidence of increased GC risk among subjects with GSTM1 null genotype, while a borderline significant association between the GSTT1*0/0 and increased GC risk emerged in uni-and multivariate analyses adjusted for possible confounders, as reported by previous studies. 18,19 The risk associated with the GSTT1 null genotype tended to vary also with age at diagnosis, with a higher risk at younger ages.…”

Section: Discussionsupporting

confidence: 75%

“…On the other hand several studies, mostly carried out in Asian populations (for which a higher prevalence of the GSTT1 null genotype has been reported), did not find any association between the GST null genotypes and increased GC risk. [24][25][26][27][28][29] Recently, a strong significant association between the GSTT1 null genotype and increased risk of another gastric neoplasia (marginal zone lymphoma) was observed in a case-control study carried out in England. 30 The interaction between GSTM1 and GSTT1 null genotypes has only been explored in 2 studies, with no evidence of departure from a multiplicative model, possibly because of the small size (91 and 136 GC cases, respectively).…”

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confidence: 99%

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GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population

Palli

Saieva

Gemma

et al. 2005

Intl Journal of Cancer

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Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p ¼ 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR ¼ 2.27; 95% CI: 1.14-4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p ¼ 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. ' 2005 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 75%

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confidence: 99%

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population

Palli

Saieva

Gemma

et al. 2005

Intl Journal of Cancer

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“…Deletion of GSTT1 was found not to be associated with gastric cancer risk in several studies in a variety of populations (17,(20)(21)(22)(23)(24)(25)(26)(27). One study in Poland found a significant increase in risk for null GSTT1 limited to cases with age <50 years (28); another study in China reported a significant OR of 2.5 for GSTT1 deletion (29).…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Metabolic Genes Related to Tobacco Smoke and the Risk of Gastric Cancer in the European Prospective Investigation into Cancer and Nutrition

Agudo¹,

Sala

Pera³

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus À3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis. (Cancer Epidemiol Biomarkers Prev

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“…The relationship between GSTT1, GSTM1 and CYP2E1 gene polymorphisms and the risk for gastric cancer is not obvious. Many investigations were conducted on Asian populations [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] . The Brazilian population is characterized by heterogeneous ethnic groups, emphasizing the need to investigate the frequency of these metabolizing genes and their association with gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

GSTT1,GSTM1andCYP2E1genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

Colombo

Rossit²,

Caetano³

et al. 2004

WJG

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AIM:To test the hypothesis that, in the Southeastern Brazilian population, the GSTT1, GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC), 100 cases of chronic gastritis (CG), and 150 controls (C). Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR. CYP2E1/PstI genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups. However, a significant difference between CG and C was observed, due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group. The GSTT1 null genotype occurred more frequently in Negroid subjects, and the GSTM1 null genotype in Caucasians, while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1, GSTM1 and CYP2E1 polymorphisms and gastric cancer.Colombo J, Rossit ARB, Caetano A, Borim AA, Wornrath D, Silva AE. GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population.

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Prognostic potential of glutathione S-transferase M1 and T1 null genotypes for gastric cancer progression

Cited by 44 publications

References 38 publications

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high‐risk italian population

Polymorphisms in Metabolic Genes Related to Tobacco Smoke and the Risk of Gastric Cancer in the European Prospective Investigation into Cancer and Nutrition

GSTT1,GSTM1andCYP2E1genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

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