Breast cancer progression and host polymorphisms in the chemokine system : role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele

This study is the first to implicate host chemokine gene variants in the progression of breast cancer. Analysis of polymorphisms in the chemokine system indicated that breast cancer patients carrying at least one G allele for the MCP-1 gene regulatory region were at increased risk of developing metastases independently of the initial stage. We observed no correlation with RANTES, SDF-1, and CCR5 polymorphisms. Macrophage infiltration is a cornerstone of inflammation and neoangiogenesis, which negatively affect prognosis of invasive breast cancer (8 ). Therefore, any variation accelerating transcriptional activity in genes encoding for proteins involved in macrophage infiltration could be suspected to enhance tumor progression and metastasesIn a previous study, we reported a correlation between a functional matrix metalloproteinase-3 (MMP-3) gene polymorphism, the more active 5A variant, and breast cancer susceptibility and found that 5A homozygosity is an independent factor of poorer prognosis (36 ). The results reported here seem to run in the same direction because protease production (including MMP-3) is one of the protumor biological functions of TAMs (20 ) that are recruited and activated by MCP-1. Although suggestive and consistent with our hypothesis, the present results must be considered cautiously. Further studies are needed to confirm the role of a functional MCP-1 gene SNP regarding the relationships between breast cancer and host. This is a very complex matter involving an incredibly high number of variables, each of which may influence in some degree this relationship. Functional MCP-1 gene SNPs represent only one of many factors involved in determining the prognosis of breast cancer. Should our data be confirmed, in the future MCP-1 could be a reliable candidate for inclusion in a panel of genetic risk factors conditioning the course of the disease.