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RESEARCH PRODUCT

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

Robert ZeillingerIngrid BergerSepp LeodolterClemens B. TempferLukas HeflerChristoph GrimmHeinz KoelblNicole ConcinCaroline Tomovski

subject

AdultSialoglycoproteinsBiologyBioinformaticsmedicine.disease_causePolymerase Chain ReactionExonGene clustermedicineHumansPromoter Regions GeneticAllelesAgedNeoplasm StagingAged 80 and overVulvar neoplasmPolymorphism GeneticVulvar NeoplasmsObstetrics and GynecologyInterleukinExonsMiddle AgedVulvar cancermedicine.diseaseInterleukin 1 Receptor Antagonist ProteinCell Transformation NeoplasticInterleukin 1 receptor antagonistOncologyIL1AMultigene FamilyCarcinoma Squamous CellCancer researchFemaleCarcinogenesisInterleukin-1

description

Abstract Objective . The interleukin-1 (IL-1) family, that is, IL-1α and β 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-1α gene ( IL1A C[−889]T), the IL-1β 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.

https://doi.org/10.1016/j.ygyno.2003.11.039