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Laryngorhinootologie 2002; 81(6): 406-412
DOI: 10.1055/s-2002-32208
Onkologie
© Georg Thieme Verlag Stuttgart · New York

Einfluss von Glutathion S-Transferase und Cytochrom P450 Genpolymorphismen auf das Verhalten von Kopf-Hals-Karzinomen

Influence of Glutathione S-Transferase and Cytochrome P450 Polymorphisms on Prognosis of Head and Neck CancerC.  Matthias 1 , V.  Jahnke 1 , A.  A.  Fryer 2 , R. C.  Strange 2
  • 1HNO-Klinik und Poliklinik der Charité (Direktor: Prof. Dr. V. Jahnke), Humboldt-Universität Berlin
  • 2Clinical Biochemistry Research Group (Head: Prof. R.C. Strange, PhD), School of Postgraduate Medicine, Keele University, Staffordshire, England
Further Information

Publication History

13. Juli 2001

26. November 2001

Publication Date:
13 June 2002 (online)

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Zusammenfassung

Hintergrund: Die polymorphen Genorte der entgiftenden Enzyme Glutathion S-Transferase und Cytochrom P450 sind neben ihrer klassischen Rolle als risikobeeinflussende Genvariationen mit der Prognose von Tumorerkrankungen in Verbindung gebracht worden. Methode: Wir beschreiben den Einfluss von GST- und CYP-Polymorphismen auf die Prognoseparameter initialer Tumorausdehnung, initialer Halslymphknotenbefall, histologischer Differenzierungsgrad und das rezidivfreie Überleben über fünf Jahre. Ergebnisse: GSTT1 0 war mit fortgeschrittenen und lymphogen metastasierten Pharynxkarzinomen assoziiert. CYP2D6 PM war mit einem malignen Halslymphknotenbefall assoziiert. Eine Beeinflussung der 5-Jahresheilung durch ein einzelnes Gen konnte nicht nachgewiesen werden. Schlussfolgerungen: Erstmalig konnten genetisch determinierte Wirtsfaktoren an den Genorten der entgiftenden Enzyme mit prognostisch wichtigen Faktoren der Kopf-Hals-Tumorerkrankung in Verbindung gebracht werden.

Abstract

Background: The polymorphic gene loci of the detoxifying enzymes GST and CYP are susceptibility factors for head and neck cancer. Recently, they have been associated with outcome in several cancers. Methods: Accordingly, we have examined, in patients with squamous cell carcinoma (SCC) of the head and neck, associations between GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1 and CYP2E1 genotypes and outcome parameters, tumor extension, histological grade, presence of lymph nodes, and recurrence free survival over 5 years. Genotypes were determined by PCR; logistic regression and a step-wise model were used to investigate the influence of the individual genes. Results: GSTT1 0 was associated with T3/T4 tumor lesions in the pharynx and oral cavity (p = 0.029), but not laryngeal SCC cases. GSTT1 0 was also associated with histological differentiation (G3) in the oral cavity /pharynx, but not laryngeal SCC cases, although this association only approached significance (p = 0.069). CYP2D6 PM and HET were associated with lymph node involvement in the laryngeal SCC cases. Conclusions: The data demonstrate site-dependent associations between GSTT1 null and CYP2D6 PM and tumor extension and lymph node involvement in SCC of the head and neck.

Schlüsselwörter

Glutathion S-Transferase - Cytochrom P450 - Larynxkarzinom - Pharynxkarzinom - Tumorprognose

Key words

Glutathione S-transferase - Cytochrome P450 - Pharyngeal cancer - Laryngeal cancer - Cancer prognosis

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Priv.-Doz. Dr. C. Matthias

HNO-Klinik der Charité, Campus Virchow-Klinikum der Humboldt-Universität

Augustenburger Platz 1 · 13353 Berlin

Email: christoph.matthias@charite.de

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