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 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.


CONCLUSIONS
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.
Department of Obstetrics, University of Vienna School of Medicine, A-1090 Vienna, Austria.
Christoph
C
Grimm
Ingrid
I
Berger
Caroline
C
Tomovski
Robert
R
Zeillinger
Nicole
N
Concin
Sepp
S
Leodolter
Heinz
H
Koelbl
Clemens B
CB
Tempfer
Lukas A
LA
Hefler
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012795:Sialoglycoproteins / Q000235:genetics*; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins