Glutathione-S-Transferase M1, M3, T1 and P1 polymorphisms and susceptibility to non-small-cell lung cancer subtypes and hamartomas

Risch, Angela; Wikman, Harriet; Thiel, Stephen; Schmezer, Peter; Edler, Lutz; Drings, P.; Dienemann, H.; Kayser, Klaus; Schulz, Volker; Spiegelhalder, B; Bartsch, Helmut

doi:10.1097/00008571-200112000-00003

Cited by 73 publications

(48 citation statements)

References 38 publications

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“…Previous similar findings have lead to the hypothesis that GSTgenotypes may be important in modulating not only the detoxification of PAH-carcinogens but also the elimination of potentially chemopreventive substances contained in the diet. 25 Due to the small number of individuals this hypothesis can not be explored further in our study.…”

Section: Discussionmentioning

confidence: 92%

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Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk

Becher

Ramroth

Ahrens

et al. 2005

Intl Journal of Cancer

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Primary risk factors for laryngeal cancer are smoking and alcohol. The relevance of occupational exposures in the etiology of laryngeal cancer is not yet clarified. Some studies have suggested various occupational agents as additional causal risk factors. A population-based case-control study 1:3 frequency matched by age and gender on laryngeal cancer was carried out in southwest Germany with 257 cases (236 males and 21 females between the ages of 37-80, histologically confirmed and diagnosed between January 5, 1998 and December 31, 2000) and 769 population controls (702 males, 67 females). Occupational exposures and other risk factors were obtained with face-to-face interviews using a detailed standardized questionnaire. The complete individual work history was assessed. A detailed assessment of work conditions was obtained by job-specific questionnaires for selected jobs known to be associated with exposure to potential carcinogens. A specific substance list was used as second method for exposure assessment. Blood samples were taken from all individuals for genotype analysis. A strong effect of polycyclic aromatic hydrocarbons exposure on laryngeal cancer risk after adjustment for smoking and alcohol (odds ratio [OR] 5 5.2, 95% confidence interval [CI] 5 1.6-17.1) was observed for concordant exposure classified with both methods, and a clear dose-response (p < 0.01 for linear trend) for exposure duration. Our findings are supported by risks associated with occupational groups in which this exposure is a priori considered likely. A differential effect by glutathione-S-transferases-M1 genotype was found, however, small numbers do not allow firm conclusions on effect modification. Our study contributes to classifying polycyclic aromatic hydrocarbons as a risk factor for laryngeal cancer. ' 2005 Wiley-Liss, Inc.Key words: case-control studies; gene-environment interaction; glutathione-S-transferases; laryngeal cancer; occupational exposure; road construction workers Laryngeal cancer is the second most common cancer of the respiratory tract with an age standardized (Segi World population) incidence rate for the year 2000 of about 10 in 100,000 in males and 1 in 100,000 in females in Europe. The range is from 2.1 (Sweden) to 16 (Belarus) in males, and from 0.18 (Latvia) to 1.6 (Macedonia) in females. 1 According to recent data, 2 the crude incidence in Germany is 7 in 100,000 in males and 1 in 100,000 in females. The mortality is considerably lower because of the relatively good prognosis. Most tumors are squamous cell carcinomas.Major risk factors are smoking and extensive alcohol consumption. There is clear evidence that laryngeal cancer is causally associated with cigarette smoking. The risk increases substantially with duration and number of cigarettes smoked and relative risks (RR) up to 60 for smoking >40 cigarettes/day have been reported. 3 A few studies also reported that RR for cancer of the larynx increased with decreasing age at start of smoking. The RR decreased with increasing time since quitting smok...

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Section: Discussionmentioning

confidence: 92%

“…23,24 Gene-environment interactions have been investigated with smoking as the primary environmental variable and do not show a clear picture. 23, 24 In a case-control study on lung cancer, Risch et al 25 reports a protective effect for the GSTT1 null genotype. An interaction with smoking exposure, however, was not found.…”

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Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk

Becher

Ramroth

Ahrens

et al. 2005

Intl Journal of Cancer

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“…Homozygosity for GSTM1-null, homozygosity for GSTT1-null, and the presence of GSTP1 GG were studied as independent predictors of hazard of SLE diagnosis in Cox models adjusted for date of birth, using each polymorphism as an independent predictor, and a single composite variable for altered GST enzyme function encoded by any one of these genes (36)(37)(38)54). We did not consider haplotype analysis since the GST genes are on different chromosomes; GSTM1 is on chromosome 1, GSTT1 is on chromosome 22, and GSTP1 is on chromosome 11.…”

Section: Methodsmentioning

confidence: 99%

“…The GST genes catalyze metabolic pathways for detoxification of tobacco smoke. Homozygosity for GSTM1, GSTT1, or GSTP1*GG is associated with the risk of early-onset lung cancer (36)(37)(38). GST polymorphisms have been associated with clinical SLE manifestations but not with susceptibility to SLE (39).…”

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confidence: 99%

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

Karlson¹,

Watts²,

Signorovitch³

et al. 2007

Arthritis & Rheumatism

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Objective. The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE.Methods. Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis.Results. The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P ‫؍‬ 0.03), but there was no association with proximity to 416 hazardous sites. Available data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P ‫؍‬ 0.03) in analyses limited to these sites.Conclusion. There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms.

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“…Even more interesting is the growing body of evidence that the GSTT1 deletion is actually protective in many studies. For example, the GSTT1 deletion resulted protective for renal cell cancer, 13 breast cancer, 14 bladder cancer, 15 prostate cancer, 16 urothelial cancer 17 for certain non small cell lung cancers, 18 and for some non cancer endpoints such as low birth size 19 and chronic pancreatitis. 20 A significant negative interaction was observed between GSTT1 null and lung cancer in occupationally exposed subjects.…”

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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

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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 ...

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Glutathione-S-Transferase M1, M3, T1 and P1 polymorphisms and susceptibility to non-small-cell lung cancer subtypes and hamartomas

Cited by 73 publications

References 38 publications

Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk

Occupation, exposure to polycyclic aromatic hydrocarbons and laryngeal cancer risk

Effect of glutathione S‐TRANSFERASE polymorphisms and proximity to hazardous waste sites on time to systemic lupus erythematosus diagnosis: Results from the roxbury lupus project

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

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