| Abstract |
The molecular biology of cancer is still far from being understood, with the exception of specific familial cases. Amplifications of oncogenes, and alterations in tumor suppressor and detoxification genes, by mutations or deletions appear especially important in the development of sporadic breast tumors. Tumor infiltrating lymphocytes and tumor associated macro-phages are thought to play a crucial role in tumor immune surveillance and, possibly development. The activation and recruitment of lymphocytes is regulated by chemotactic and pro-inflammatory chemokines. It has been suggested that melanoma cells evade immune surveillance through the induction of TIL cell death by SDF-1 alpha (CXCL12) and RANTES chemokines. The relevance of chemokines to malignancy extends beyond leukocyte recruitment. Animal models have shown that chemokine secretions by tumor cells can influence angiogenesis and tumor growth. Expression of angiogenic CXC chemokines by tumor cells in severe combined immunodeficient (SCID) syngenic mice has been shown to enhance tumor growth. However, the association of any kind of cancer with chemokine related genetic markers has not been examined to date. The aim of the present study was to investigate the involvement of the chemokine system in cancer by studying frequencies of chemokine related gene polymorphisms. We selected the polymorphisms: CCR2 64-I in CCR2 receptor gene, CCR5 Δ32 and CCR5 59029G-A in CCR5 receptor gene and CXCL12-3A in CXCL12 receptor gene, which are very well characterized and have a well established association with AIDS pathogenesis based on functional or statistical data. We determined the genotype frequencies of the above 4 polymorphisms in 442 cancer samples (264 breast, 68 bladder, 110 non-melanoma skin) and 361 control samples. Our data shows a statistically significant difference of the breast cancer group compared to the control group for CXCL12-3A, CCR2 64-I polymorphisms indicating that CXCL12-3A and CCR2 64-I played a possible role in the initial stages of breast cancer. No difference was identified between controls and breast cancer samples for the CCR5 Δ32 and the CCR5 59029G-A polymorphisms. In the bladder and skin cancer groups there was no statistical difference from the control group for any of the polymorphisms studied. Summarizing, our data indicates a significant involvement of the chemokine system in the development of breast cancer.
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Διερεύνηση του ρόλου των υποδοχέων χημειοκινών στον καρκίνο μαστού, δέρματος και ουροδόχου κύστης
