Einfluss von Genvariationen im Major Histokompatibilitäts-Komplex auf das Entstehungsrisiko von Plattenepithelkarzinomen im Kopf-Hals-Bereich

Zusammenfassung

Hintergrund: Neben Zigarettenrauchen und Alkoholkonsum sind genetische Faktoren in der Entstehung von Kopf-Hals-Karzinomen von Bedeutung. Kandidaten dafür sind Mikrosatelliten-Polymorphismen in den Klasse 3-Genen des Major Histocompatibility Complex (MHC), die den Tumor Nekrose Faktor (TNF) beeinflussen. Methode: In einer Fall-Kontroll-Studie wurden 113 Kontrollpersonen, 265 Larynxkarzinompatienten und 123 Patienten mit Mundhöhlen- und Pharynxkarzinomen untersucht. Die Genotypen wurden nach PCR und Elektrophorese in einem DNA-Sequenzierer bestimmt. Ergebnisse: Die Häufigkeit eines Allels (B3) war bei Larynxkarzinompatienten signifikant häufiger nachweisbar und stellt somit ein Risikoallel dar. Bei Vorliegen des homozygoten Genotyps stieg das Erkrankungsrisiko für Larynxkarzinome deutlich an. Schlussfolgerungen: Die Ergebnisse zeigen einen Einfluss von Variationen in MHC Klasse 3-Genen auf die Entstehung von Larynxkarzinomen.

Influence of Genetic Variation in the Major Histocompatibility Complex on Head and Neck Cancer Susceptibility

Background: While cigarette smoking and alcohol consumption are risk factors for squamous cell carcinomas (SCC) of the head and neck, genetic factors are also significant. The gene of tumor necrosis factor (TNF) is located in the major histocompatibility complex class III and the cytokine has pleiotropic actions some of which are anticarcinogenic. As this gene complex is polymorphic with microsatellite markers identified it is a further candidate for head and neck cancer susceptibility. Methods: We used a case-control approach to study the influence of polymorphism at the A-D markers on susceptibility in 113 controls, 265 laryngeal and 123 oral cavity/pharyngeal SCC cases. Genotypes were identified on polyacrylamide gels in an automated DNA sequencer after amplification with fluorescently-labeled primers. Results: We found no differences in allele frequencies between controls and oral cavity/pharyngeal SCC cases but the frequency of B3 was greater in the laryngeal SCC cases than controls (p = 0.004, odds ratio 2.8). Homozygosity for B3 conferred an increased risk of laryngeal cancer compared with controls (p = 0.021, odds ratio 10.8). Conclusions: The data provide the first evidence that allelism at MHC class III microsatellite markers is associated with risk to laryngeal SCC.

Schlüsselwörter:

MHC - TNF - Larynxkarzinom - Pharynxkarzinom - Mikrosatelliten - Erkrankungsrisiko

Key words:

MHC - TNF - Pharyngeal cancer - Laryngeal cancer - Susceptibility - Microsatellites

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