Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers

Matthias, Christoph; Bockmühl, Ulrike; Jähnke, V.; Jones, Peter A.; Hayes, John D.; Alldersea, Julie; Gilford, Janice; Bailey, Lisa; Bath, Joanna; Worrall, S.F.; Hand, P.; Fryer, Anthony A.; Strange, Richard C.

doi:10.1097/00008571-199804000-00001

Cited by 109 publications

(99 citation statements)

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“…GSTM3*A and *B are expressed in the brain; yet, there appears to be no direct relationship between GSTM3 expression and the incidence of astrocytomas (Hand et al, 1996). The GSTM3*AA genotype is associated with an increased risk for laryngeal squamous cell carcinoma, whereas GSTM3*BB was putatively protective (Matthias et al, 1998). In addition, GSTM3*AA was shown to occur more frequently in patients with multiple cutaneous basal cell carcinoma than GSTM3*BB (Yengi et al, 1996).…”

Section: Mu Classmentioning

confidence: 99%

Glutathione S-transferase polymorphisms: cancer incidence and therapy

2006

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The super family of glutathione S-transferases (GSTs) is composed of multiple isozymes with significant evidence of functional polymorphic variation. Over the last three decades, data from cancer studies have linked aberrant expression of GST isozymes with the development and expression of resistance to a variety of chemicals, including cancer drugs. This review addresses how differences in the human GST isozyme expression patterns influence cancer susceptibility, prognosis and treatment. In addition to the well-characterized catalytic activity, recent evidence has shown that certain GST isozymes can regulate mitogen-activated protein kinases or can facilitate the addition of glutathione to cysteine residues in target proteins (S-glutathionylation). These multiple functionalities have contributed to the recent efforts to target GSTs with novel small molecule therapeutics. Presently, at least two drugs are in latestage clinical testing. The evolving functions of GST and their divergent expression patterns in individuals make them an attractive target for drug discovery.

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Section: Mu Classmentioning

confidence: 99%

Glutathione S-transferase polymorphisms: cancer incidence and therapy

2006

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“…As a result of this mutation, the expression of GSTM3 can be influenced. The functional consequence of this is unclear, but both negative and positive regulatory effects have been suggested (6)(7)(8). However, possible influence of GSTM3 has not been studied in esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer

Jain

Kumar

Lal

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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GSTM3 is involved in detoxification of carcinogens and may be important in modulating cancer susceptibility. GSTM3 genotype frequencies were determined in peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant controls using the PCR followed by PAGE. Patients who were heterozygous carriers of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males, the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR, 2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular modulating the risk for adenocarcinoma histology and tumors of the mid and lower third region. (Cancer Epidemiol Biomarkers Prev 2007;16(1):178-81)

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“…Se cree que la coordinación de la expresión de estas dos familias enzimáticas es necesaria para garantizar la eficiencia en la desintoxicación de mutágenos como los hidrocarburos aromáticos policíclicos, las nitrosaminas, los fenoles, el cloroformo, el nitrocloroetileno, el benceno, el tolueno y otros disolventes orgánicos. Por lo tanto, con su determinación estas enzimas se convierten en biomarcadores de susceptibilidad (41)(42)(43)(44)(45).…”

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Evaluación del daño en el ADN y vigilancia biológica de la exposición laboral a solventes orgánicos, 2006

et al. 2008

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Introducción. La exposición a solventes es uno de los mayores riesgos potenciales para millones de trabajadores en el mundo; los solventes generan contaminación ambiental y desencadenan problemas de salud pública. Objetivo. Determinar los niveles de los metabolitos benceno, tolueno y xileno, los polimorfismos de las enzimas CYP2E1, GSTM1, GSTT1 y el daño del ADN mediante el ensayo del cometa. Materiales y métodos. Se llevó a cabo un estudio descriptivo de corte transversal para la determinación de polimorfismos genéticos y prueba del cometa en 90 trabajadores pertenecientes a cinco empresas. Se aplicó una encuesta, se tomaron muestras de sangre y de orina, se midieron las concentraciones de fenol, ácido hipúrico orto y meta-metilhipúrico. Se hizo el análisis estadístico y se exploraron posibles asociaciones. Resultados. El 34,4% eran trabajadores con exposición directa a solventes. En este grupo se evidenciaron concentraciones superiores a los límites permisibles en 3,3% para fenol, en 6,6% para ácido hipúrico, en 3,3% para ácido orto-metilhipúrico y en 36,7% para ácido metametilhipúrico, mayor longitud promedio de la cola del cometa (19,5 µm) y un incremento del porcentaje de células con daño medio (19,0%) (p=0,0007). El porcentaje de individuos expuestos con genotipos ausentes para las enzimas GSTT1 y GSTM1 fue de 46,7% y de 56,8%, respectivamente. Conclusión. El uso de biomarcadores de exposición, efecto y susceptibilidad, se ha convertido en una herramienta fundamental para la evaluación del riesgo asociado con la exposición a agentes tóxicos.Palabras clave: daño del ADN/genética, exposición profesional, solventes/toxicidad, salud pública DNA damage assessment and biological monitoring of occupational exposure to organic solvents, 2006Introduction. Exposure to solvents is one of the highest potential risks for millions of workers in the world; they can generate substantial environmental pollution leading to outbreaks of public health problems. Objective. Blood levels were determined for metabolites of benzene, toluene and xylene, and polymorphisms for enzymes CYP2E1, GSTM1, GSTT1 were characterized. Damage to DNA was assessed by the comet assay for exposure to organic solvents. Materials and methods. A cross-sectional study was undertaken in 90 employees from 5 different companies. A survey form was administered; blood was sampled to detect the genetic polymorphisms and to apply the comet assay (single cell gel electrophoresis) to detect DNA fragmentation. The concentrations of phenol, ortho and meta methylhippuric acids were measured in urine. Statistical analyses explored the possible associations. Results. The percentage of workers directly exposed to solvents was 34.4%. In this group, the evidence indicated concentrations higher than the permitted limits: 3.3% for phenol, 6.6% for

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Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers

Cited by 109 publications

References 0 publications

Glutathione S-transferase polymorphisms: cancer incidence and therapy

Glutathione S-transferase polymorphisms: cancer incidence and therapy

Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer

Evaluación del daño en el ADN y vigilancia biológica de la exposición laboral a solventes orgánicos, 2006

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