INFLUENCE OF TUMOR-NECROSIS-FACTOR MICROSATELLITE POLYMORPHISMS ON SUSCEPTIBILITY TO HEAD AND NECK-CANCER

While cigarette smoking and alcohol consumption are recognized covaria tes far head and neck squamous cell carcinoma (SCC). thr role of genet ic factors in determining individual susceptibility is unknown. The hu man tumour necrosis factor (TNF) region on chromosome 6p21 within the major histocompatibility complex (MHC) includes a number of immunologi cally important genes. Recently, Eve microsatellite markers have been described in the TNF locus. TNF levels vary with different TNF microsa tellite alleles, aad associations of these microsatellite markers with autoimmune diseases and different types of cancer have been shown. Th erefore, thr TNF locus represents candidate susceptibility genes far h ead and neck cancer. This study describes tile influence of TNF and mi crosatellite polymorphisms on susceptibility to head and neck cancer b y comparing the allele frequencies of 269 patients suffering from lary ngeal cancer and 123 patients suffering from oral cavity/pharyngeal ca ncer and 113 German controls. DNA was extracted from peripheral blood samples. amplified by polymerase chain reaction with fluorescently lab elled primers for TNF microsatellite (a-d) and electrophoresed on poly acrylamide gels using au automated DNA sequencer. The data showed no d ifferences in allele frequencies between controls anti pharyngeal canc er patients. By contrast, the TNF b3 allele was associated with altere d risk for laryngeal cancer (p = 0.0006, edits ratio 2.2). Homozygosit y for TNF b3/b3 resulted in an increased risk of developing laryngeal cancer (p = 0.004, odds ratio 5.3). Susceptibility to supraglottic SCC and multiple primary tumours was mediated by the absence of thp all a llele. The data provide the first evidence that allelism at the TNF mi crosatellite markers alter the risk of developing SCC of the larynx.