Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review

Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer.None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised.Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.The role of cytokines in cancer immunity and carcinogenesis in general has been well established [1]. Single nucleotide polymorphisms in specific candidate genes are thought to influence expression and/or activity of the encoding proteins thereby predisposing to solid cancers especially breast cancer [2]. Many cytokine polymorphisms have been studied for associations with susceptibility to gastric cancer [3-5], liver cancer [6,7], lung cancer[8], prostate cancer [9] and ovarian cancer [10] with mixed results.The cytokines of the IL-1 family [11], IL-4 and its receptor [12,13], IL-6 [14,15] and IL-10 [16,17] are important candidate genes as they play an important role in breast cancer pathogenesis. IL1-alpha promotes growth of breast cancer cells and cachexia [18]. In breast cancer cells, IL1-beta increases the transcriptional activity of ER-alpha [19] which is a prognostic factor in breast cancer and the expression and stabilisation of IL-8 RNA [20] which is a potent angiogenic factor. IL-4 inhibits tumour growth by its anti-angiogenic effect [21] and inhibits growth and induces apoptosis of breast cancer cell lines in the pr