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Interleukin-1 and Interleukin-6 Gene Polymorphisms and the Risk of Breast Cancer in Caucasian Women

Authors' Affiliations: ¹ Department of Obstetrics and Gynecology, ² Core Unit for Medical Statistics and Informatics, Medical University of Vienna, and ³ Ludwig Boltzmann Institute for Gynecology and Gynecologic Oncology, Vienna, Austria; ⁴ Departments of Obstetrics and Gynecology, Martin-Luther-University Medical School Halle-Wittenberg, Halle; and ⁵ Johannes Gutenberg-University Mainz, Mainz, Germany

Requests for reprints: Lukas A. Hefler, Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-2962; Fax: 43-1-40400-2911; E-mail: lukas.hefler{at}meduniwien.ac.at.

Purpose: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown.

Experimental Design: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [–889 C/T polymorphism of the IL1 gene (IL1A), –511 C/T polymorphism of the IL1ß promoter (IL1B promoter), a polymorphism of IL1ß exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the –174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing.

Results: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables.

Conclusions: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the –174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.

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