The Tumour Necrosis Factor (TNF) locus lies within the MHC locus on human chromosome 6. It encompasses the genes for TNF, Lymphotoxin alpha (LTalpha) and Lymphotoxin Beta (LTbeta). The location of the locus has intimated a role for TNF in the progression of MHC-linked and also malignant diseases. Ten polymorphic sites have been detected within the locus (comprising of RFLPs and microsatellites) and consequently, disease-associated alleles are now being looked for. Certain alleles have been linked to increased levels of TNF expression and these higher levels are thought to contribute to the aetiology of disease states. In this study I have examined six of the polymorphic sites spanning the TNF locus in 84 unrelated breast cancer patients, presenting at a follow-up clinic in Glasgow Royal Infirmary. I obtained allelotype and genotype data on each individual and compared the results with those previously obtained within our group for two further adenocarcinoma populations (gastric, n=45 and colorectal, n=106) and a control population, n=115. The results show that there is not a defined malignant genotype at the TNF locus, but the breast population does differ significantly to the control population in allelotype expression at two of the polymorphic sites, the TNFc and TNFa microsatellites (p=0.0282 and 0.0023 respectively). The colorectal cancer population is significantly different to the controls with regard to allelotype expression at the TNFc locus (p=0.0111) and also shows a significantly different genotype expression pattern at this site (p=0.0248) (data supplied by group member, Hui-Hui Oh). I also found that, in the breast cancer population, there was an overexpression of two alleles and a genotype previously demonstrated to be associated with high TNF expression; TNFa2, TNFc2 and the TNFB*1, B*2 genotype at a Nco-1 endonuclease RFLP site. This leads us to suggest that the predicted higher levels of TNF in these patients may play a role in the progression to the malignant state
