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Editor—TNFα (tumour necrosis factor-alpha) is a cytokine produced by macrophages and monocytes with a wide range of activities, and polymorphisms within this gene have been postulated to contribute to MHC associations with autoimmune and infectious diseases.1 The role of TNFα in cancer is a controversial matter, because while it plays a key role in the “in vitro” killing of tumour cells by macrophages and lymphocytes, it has also been found in high concentrations in patients with cancer, suggesting that it may be an endogenous tumour promoter “in vivo”.2 3 Different results with several tumour types show that TNFα may have both tumour necrotic and tumour promoting activities.
Recently, several genetic polymorphisms have been described in the human TNFα promoter.4-6Among them, the rare allele at position −308 (TNF308.2) has been proven to be part of a complex haplotype that is involved in higher TNFα levels and has been related to poor prognosis in several diseases.7 The existence of differentTNFα alleles, related to different levels of TNFα, raises the possibility that tumour development is somewhat related to the genetic propensity of the person to produce higher levels of TNFα and, therefore, with the presence of genetic variants in this gene. In fact, an increase in the TNF308.1/TNF308.2 genotype has been reported in different tumour types, with a significantly increased frequency of the TNF308.2 allele in patients with malignant tumours.8 Wilson et al 7 have shown that the polymorphism at −308 has a significant effect on the transcriptional activity of the humanTNFα gene, either because the interaction of the transcription enhancers is increased owing to the different DNA conformations, or because the TNF2 variant is the target for novel binding proteins.
The G to A transition at position –238 (TNF238.2) is also suspected …