Interleukin-1 receptor antagonist gene polymorphism in epithelial ovarian cancer

The development of malignant tumors is constituted by different immunological components. Interleukin (IL)-1 receptor antagonist (RA) is known to be critically involved in the carcinogenesis of different malignant solid tumors. Polymorphism of a specific gene can have an important effect on gene transcription, the stability of the mRNA, or the quantity and activity of the resulting protein. In a case-control study, we investigated the polymorphism of the IL-1RA gene in 162 women with histologically proven ovarian cancer and 121 patients with benign gynecological diseases. Overall, 25.9% of the patients were diagnosed in International Federation of Gynecologists and Obstetricians (FIGO) stage I or II, and 74.1% of the patients were diagnosed in FIGO stage III or IV (study group). The distribution of genotype frequencies was significantly different between study and control group with respect to allele 1/2 heterozygotes (32.1% versus 14.9%; P < 0.001). Furthermore, patients who were heterozygous at allele 2 for IL-1 RA (IL-RA 1/2) had a significantly higher risk for ovarian cancer with an odds ratio of 2.7 (95% confidence interval, 1.5-4.9). There were no differences between IL-1 RA 1/2 polymorphism and other alleles in clinical parameters (e.g., tumor stage, histological type, and recurrence status). Allele 2 polymorphism of the IL1-RA gene seems to be one of the critical points in the molecular pathway of different malignant diseases. This allele seems to play an additional role in the occurrence of ovarian cancer and should be further investigated for screening and risk evaluation.