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

Abstract

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 tumorigenic and tumoricidal 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.