title: Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308.
abstract: The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to play a central role. A single base pair polymorphism at position --308 in the promoter region of the TNF-alpha gene associated with an enhanced secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were compared. For the TNF--308 polymorphism there was significant association between the genotype or allele frequencies and having BCC. To determine whether patients with a previous BCC had an increased capacity to secrete TNF-alpha, mononuclear cells were stimulated with lipopolysaccharide. Mononuclear cells from patients with a previous BCC (n=15) demonstrated a significantly increased release of TNF-alpha upon stimulation with lipopolysaccharide (P<0.03) compared with mononuclear cells age-matched control subjects (n=16). Further studies of other polymorphisms of the TNF-alpha gene associated with increased TNF-alpha production and BCC and necessary.
authors.affiliation: Department of Dermatology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. lskov@dadlnet.dk
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: Bo
authors.initials: B
authors.lastname: Bang
authors.forename: David
authors.initials: D
authors.lastname: Francis
authors.forename: Jonathan N W N
authors.initials: JN
authors.lastname: Barker
authors.forename: Ole
authors.initials: O
authors.lastname: Baadsgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D004247:DNA