A polymorphism of the interleukin-1 receptor antagonist plays a prominent role within the interleukin-1 gene cluster in vulvar carcinogenesis

Objective. The interleukin-1 (IL-1) family, that is, IL-1alpha and beta and the IL-1 receptor antagonist (IL-1RA), is known to modulate various tumorgenic and tumorcidal effects in humans. Its biological function in squamous cell carcinogenesis of various anatomical sites has been stressed. Although various studies showed a certain association between genes encoding the IL-1 family and human malignancies, no data with respect to vulvar cancer have been published to date. Methods. We ascertained four polymorphisms of the IL-1alpha gene (IL1A C[-889]T), the IL-1beta gene (IL1B promoter C[-511]T and IL1B exon 5 position +3953), and the IL-1RA gene (IL1RN intron 2) in 68 patients with surgically treated squamous cell vulvar cancer and 228 healthy Caucasian controls. Results. Presence of the minor allele of the IL1RN polymorphism was found to be protective for vulvar cancer [odds ratio (OR) 0.5, P= 0.03], the other investigated polymorphisms showed no association with the disease and the investigated clinicopathological parameters. In a multivariate analysis, only the established prognosticators were associated with patients' survival. Conclusion. We are the first to report on polymorphisms in genes encoding cytokines in patients with vulvar cancer. Reflecting its biological role, the common IL1RN intron 2 polymorphism seems to play a prominent role within the IL-1 gene cluster with respect to vulvar carcinogenesis. (C) 2004 Elsevier Inc. All rights reserved.