Influence of Tumour Necrosis Factor Microsatellite Polymorphisms on Susceptibility to Head and Neck Cancer

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Abstract
While cigarette smoking and alcohol consumption are recognized covariates for head and neck squamous cell carcinoma (SCC), the role of genetic factors in determining individual susceptibility is unknown. The human tumour necrosis factor (TNF) region on chromosome 6p21 within the major histocompatibility complex (MHC) includes a number of immunologically important genes. Recently, five microsatellite markers have been described in the TNF locus. TNF levels vary with different TNF microsatellite alleles, and associations of these microsatellite markers with autoimmune diseases and different types of cancer have been shown. Therefore, the TNF locus represents candidate susceptibility genes for head and neck cancer. This study describes the influence of TNF a-d microsatellite polymorphisms on susceptibility to head and neck cancer by comparing the allele frequencies of 269 patients suffering from laryngeal cancer and 123 patients suffering from oral cavity/pharyngeal cancer and 113 German controls. DNA was extracted from peripheral blood samples, amplified by polymerase chain reaction with fluorescently labelled primers for TNF microsatellite (a-d) and electrophoresed on polyacrylamide gels using an automated DNA sequencer. The data showed no differences in allele frequencies between controls and pharyngeal cancer patients. By contrast, the TNF b3 allele was associated with altered risk for laryngeal cancer (p=0.0006, odds ratio 2.2). Homozygosity 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 the a11 allele. The data provide the first evidence that allelism at the TNF microsatellite markers alter the risk of developing SCC of the larynx.