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Polymorphisms of the Interleukin-1 Gene Cluster and Ovarian Cancer

Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria; Department of Obstetrics and Gynecology, Martin-Luther-University Halle-Wittenberg, Halle, Germany; Department of Obstetrics and Gynecology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Viennia, Austria lukas.hefler{at}akh-wien.ac.at

Elisabeth Ludwig, MD

Antje Lebrecht, MD

Robert Zeillinger, PhD

Dan Tong-Cacsire, MD

Heinz Koelbl, MD

Sepp Leodolter, MD

Clemens B. Tempfer, MD

Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria; Department of Obstetrics and Gynecology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

Objective: Interleukin-1 (IL-1) is known to be critically involved in ovarian carcinogenesis. We investigated a panel of polymorphisms of the IL-1 and the IL-1 receptor antagonist (IL-1 RA) genes in patients with ovarian cancer.

Methods: One hundred thirty-four patients with surgically staged ovarian cancer, 27 patients with borderline ovarian cancer, and 134 healthy controls were genotyped for three polymorphisms of the IL-1 gene (-889 C/T polymorphism of the IL-1alpha gene [IL1A], -511 C/T polymorphism of the IL-1beta promoter [IL1B promoter], a polymorphism of IL-1beta exon 5 [IL1B exon 5]), and an 86-base pair repeat in intron 2 of the IL-1 RA gene [IL1RN]) using polymerase chain reaction and pyrosequencing.

Results: Allelic frequencies did not differ between patients with ovarian cancer and controls. In the ovarian cancer group, polymorphism did not correlate with any of the investigated clinicopathologic variables, including tumor stage, lymph node, and histologic grade. In univariate and multivariate models, there was no correlation between any polymorphism and patients' overall and disease-free survival.

Conclusion: We investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of IL1A, IL1B, and IL1RN and the occurrence of ovarian cancer. Allelic variation within the IL-1 gene clusters does not seem to play a role in ovarian carcinogenesis and does not appear to be a useful tool for possible screening and risk evaluation.

Key Words: Interleukin-1 • polymorphism • ovarian cancer

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