Meta- and Pooled Analysis of GSTT1 and Lung Cancer: A HuGE-GSEC Review

Raimondi, Sara; Paracchini, Valentina; Autrup, Herman; Dios, Juan Miguel Barros; Benhamou, Simone; Boffetta, Paolo; Coté, Michele L.; Dialyna, I. A.; Dolžan, Vita; Filiberti, R.; Garte, Seymour; Hirvonen, Ari; Husgafvel‐Pursiainen, Kirsti; Imyanitov, E. N.; Kalina, I; Kang, Daehee; Kiyohara, Chikako; Kohno, Takashi; Kremers, Pierre; Lan, Qing; London, Stephanie J.; Povey, Andrew C.; Rannug, Agneta; Reszka, Edyta; Risch, Angela; Romkes, Marjorie; Schneider, Joachim; Seow, Adeline; Shields, Peter G.; Sobti, Ranbir Chander; Sørensen, Mette; Spinola, Monica; Spitz, Margaret R.; Strange, Richard C.; Stücker, Isabelle; Sugimura, Haruhiko; To‐Figueras, Jordi; Tokudome, Shinkan; Yang, Ping; Yuan, Jian‐Min; Warholm, Margareta; Taioli, Emanuela

doi:10.1093/aje/kwj321

Cited by 128 publications

(87 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The frequency of GSTM1-null genotypes in the control population (47.2%) in the present study was similar to what was published previously in metaanalyses and pooled analyses among Caucasians (21)(22)(23). However, the frequency of GSTT1-null geno type in our cohort (27.6%) was higher than the values repor ted among Caucasians (18.1%) (24).…”

Section: Discussionsupporting

confidence: 89%

The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma

Ćorić¹,

Plješa-Ercegovac²,

Matić³

et al. 2010

Journal of Medical Biochemistry

View full text Add to dashboard Cite

izolovana iz krvi 182 kontrolna subjekta i 76 bolesnika sa KBP. Polimorfizam GSTM1 i GSTT1 je odre|ivan metodom PCR-a. Dobijeni rezultati su analizirani u odnosu na faktore rizika za KBP, uklju~uju}i pu{enje i profesionalnu izlo`e nost. U~estalost GSTM1-nultog genotipa je bila vi{a kod bolesnika sa KBP (60,5%) nego kod kontrola (47,2%). Prisustvo GSTT1-nultog genotipa je utvr|eno kod 28,6% kontrola i 27,6% bolesnika sa KBP. Nosioci GSTM1-nultog genotipa imaju 1.9-puta ve}i rizik za KBP (95% CI: 1,06-3,33). Prisustvo GSTT1 aktivnog genotipa je udru `eno sa pove}anim rizikom za KBP kod profesionalno izlo `enih subjekata ka da su kao referentna grupa uzeti neizlo`eni nosici GSTT1-nultog genotipa (OR: 2,48; 95% CI: 1,05-5,86). Nije otkrivena povezanost izme |u nedo statka aktivne forme GSTM1 i GSTT1 i pu{e -nja kod obolelih od KBP. Studija izvedena u Srbiji je pokazala da prisustvo GSTM1 aktivnog genotipa {titi od nastanka KBP, dok prisustvo GSTT1 aktivnog geno tipa pove}ava rizik kod profesionalno izlo`enih osoba.Klju~ne re~i: faktori rizika, glutation S-transferaze, karcinom bubre`nog parenhima, polimorfizamList of non-standard abbreviations: GST -glutathione S-transferase; RCC -renal cell carcinoma; OR -odds ratio, CIconfidence interval Summary: Members of the glutathione S-transferase (GST) superfamily exhibit polymorphic expression. GSTs are investigated as biomarkers of risk for various cancers, including renal cell carcinoma (RCC). The aim of this study was to test the association between GSTM1 and GSTT1 polymorphism and susceptibility to RCC, independently or in conjunction with known risk factors. Genomic DNA was isolated from 182 controls and 76 patients with RCC. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Data obtained were analyzed with respect to RCC risk factors including smoking and occupational exposure. The frequency of GSTM1-null genotype was higher in patients with RCC (60.5%) compared to controls (47.2%). GSTT1-null genotype was found in 28.6% controls and 27.6% of cases. GSTM1-null individuals exhibit 1.9-fold increased risk of RCC (95% CI: 1.06-3.33). The presence of GSTT1 active genotype was associated with increased risk of RCC in occupationally exposed sub jects when unexposed GSTT1-null subjects were used as a comparison group (OR: 2.48; 95% CI: 1.05-5.86). No association was found between the inactive form of GSTM1 and GSTT1 and smoking in RCC patients. In a Serbian cohort of patients, the presence of a GSTM1 active geno type is protective against RCC, whereas a GSTT1 active geno type increases RCC risk in occupationally exposed subjects.

show abstract

Section: Discussionsupporting

confidence: 89%

The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma

Ćorić¹,

Plješa-Ercegovac²,

Matić³

et al. 2010

Journal of Medical Biochemistry

View full text Add to dashboard Cite

show abstract

“…In the present meta-analysis, under the light of a nearly 3-fold increase in the number of eligible studies, a clear association between GSTT1 null genotype and increased breast cancer risk became evident and seemed indeed confined to non-Chinese populations. Race-specific effects of GSTT1 polymorphism status may not seem surprising at a meta-analytical level, as racespecific associations have been described in meta-analyses examining lung [73] and gastric [74] cancer.…”

Section: Discussionmentioning

confidence: 99%

GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis

Sergentanis

Economopoulos

2009

Breast Cancer Res Treat

View full text Add to dashboard Cite

Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes; studies have principally examined mu-1 (GSTM1: null/present), theta-1 (GSTT1: null/present) and pi-1 (GSTP1 Ile105Val) gene polymorphisms concerning breast cancer risk. Regarding GSTT1 and GSTP1 polymorphisms, studies remain controversial and no recent meta-analysis has appeared. This meta-analysis aims to examine whether GSTT1 and GSTP1 polymorphisms are associated with breast cancer risk. Separate analyses were performed on Chinese and non-Chinese populations, in an attempt to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to August 2009. Regarding GSTT1 null/present genotype, 41 case-control studies were eligible (16,589 breast cancer cases and 19,995 controls); 30 case-control studies were eligible for GSTP1 Ile105Val (16,908 cases and 20,016 controls). Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. At the overall analysis, the null GSTT1 genotype was associated with elevated breast cancer risk (pooled OR=1.114, 95%CI: 1.035-1.199, random effects). However, the association seemed confined to non-Chinese populations (33 studies, pooled OR=1.128, 95%CI: 1.042-1.221, random effects), given that the association was not significant in the subset of Chinese studies (eight studies, pooled OR=1.061, 95%CI: 0.875-1.286, random effects). Regarding GSTP1 Ile105Val, no statistically significant associations were detected in non-Chinese populations (25 studies). On the other hand, the GG genotype was associated with increased breast cancer risk in Chinese populations (five studies, pooled OR=1.297, 95%CI: 1.023-1.645, fixed effects); accordingly, the recessive model yielded statistically significant results (pooled OR=1.273, 95%CI: 1.006-1.610, fixed effects). In conclusion, polymorphisms of both 3 GSTT1 and GSTP1 genes seem associated with elevated breast cancer risk in a racespecific manner. Given the small number of Chinese studies, the finding on GSTP1 Ile105Val merits further investigation.

show abstract

“…[7][8][9][10] Careful analysis of the literature reveals a much more murky picture for the GSTT1 gene than for GSTM1. Although one group reported GSTT1 to be a risk factor for lung cancer, 11 the majority of studies have found no association between GSTT1 deletion and cancer as shown by a meta and pooled analysis, 12 and in general there are more negative findings for this variant than for the GSTM1 deletion. Even more interesting is the growing body of evidence that the GSTT1 deletion is actually protective in many studies.…”

mentioning

confidence: 99%

“…20 A significant negative interaction was observed between GSTT1 null and lung cancer in occupationally exposed subjects. 12 Speculations as to the mechanism of the protective effect of GSTT1 in human cancer have largely focused on the possibility that the products of GSTT1 conjugating reactions could produce in certain instances more carcinogenic metabolites, such as for the dihalomethanes and other chlorinated hydrocarbons, [21][22][23][24] which are known to be bioactivated by GSTT1. In addition, since the GST genes use certain chemopreventive compounds such as isothiocyanates as substrates, the deletion of GSTT1 could lead to the availability of higher levels of cancer preventing compounds.…”

mentioning

confidence: 99%

Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans

Garte

Taioli

Popov

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

A useful approach for studies on the mechanisms of genetic variation in cancer susceptibility is to use intermediary biochemical endpoints with mechanistic relevance to the genes under study. We examined the effects of individual genotype at seven metabolic gene loci on a marker of oxidative DNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine, in people exposed to polycyclic aromatic hydrocarbons (PAH) from three Central European cities. The GSTT1 homozygous deletion variant was associated with a significant protective effect for exposure to total PAHs and to eight specific PAHs, although the magnitude and significance of the effect varied among these compounds. Categorical sensitivity analysis was used to determine that the frequency of the GSTT1 deletion was significantly higher in people who proved to be more resistant to the DNA damaging effects of PAH exposure than in people who were the most sensitive. There is a growing literature on the protective effect of GSTT1 deletion in both disease and intermediary endpoints related to environmental carcinogenesis. The mechanism for this effect might be related to specific PAH substrate specificities, or could be related to other functions of GSTT1 gene in oxidative stress induced damage pathways. ' 2007 Wiley-Liss, Inc.Key words: biological markers; susceptibility; cohort studyThe paradigm of gene-environment interactions in carcinogenesis holds that genetic variation in loci responsible for the metabolism of carcinogens should be reflected in the well known variability in risk of cancer among exposed populations. This principle has been confirmed in some instances, but not in others, 1-4 mostly using case control approaches. One of the most studied metabolic gene families in this context is the glutathione-S-transferases (GST), which code for a family of phase II conjugating enzymes, generally considered to be involved in detoxification. 5,6 Since many classical electrophilic carcinogens are substrates for the GST enzymes, it has generally been hypothesized that the common human polymorphic variants of these genes, which for GSTM1 and GSTT1 are homozygous deletions, should result in a decrease in conjugation and subsequent elimination of carcinogenic intermediates, with the result of increasing the dose of carcinogen to target tissue. Individual case control studies, as well as pooled and meta analyses have confirmed this hypothesis to some extent, so that for example the deletion of GSTM1 variant was found to be associated with various cancer types, both alone and in combination with other genetic polymorphisms. 7-10 Careful analysis of the literature reveals a much more murky picture for the GSTT1 gene than for GSTM1. Although one group reported GSTT1 to be a risk factor for lung cancer, 11 the majority of studies have found no association between GSTT1 deletion and cancer as shown by a meta and pooled analysis, 12 and in general there are more negative findings for this variant than for the GSTM1 deletion. Even more interesting is the growing body of evidence that ...

show abstract

Meta- and Pooled Analysis of GSTT1 and Lung Cancer: A HuGE-GSEC Review

Cited by 128 publications

References 84 publications

The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma

The Role of GSTM1 and GSTT1 Polymorphism in Patients with Renal Cell Carcinoma

GSTT1 and GSTP1 polymorphisms and breast cancer risk: a meta-analysis

Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans

Contact Info

Product

Resources

About