Immuno-modulatory gene polymorphisms and outcome in breast and ovarian cancer

Breast and ovarian cancer continue to be a significant source of morbidity and mortality. Improved understanding of signalling pathways related to growth and apoptosis has led to targeted treatments and modest improvement in long term outcomes. However, it has become increasingly clear that tumor factors alone are not the sole determinants of outcome in patients with breast and ovarian cancer. The tumor microenvironment and other immunologic host processes play an integral role in the overall interactions between disease, host and treatment. Cytokines play a major role in the immune response to tumors. Single nucleotide polymorphisms (SNPs) in the regulatory or coding regions of many cytokine genes lead to functional alterations in the transcriptional regulation of these genes or the proteins they encode. This review examines the current literature linking functional variants in cytokine and other immune genes to outcomes in breast and ovarian cancer. We have focused on those involved in the proinflammatory response (IL-6, TNF-alpha), apoptosis (TGF-beta, Fas, FasL, C1QA), angiogenesis (IL-8) and autoimmunity (IL-10). While much remains to be learned about the mechanisms underlying these variants and their impact on tumor behavior, this area holds promise for future development of prognostic profiles and therapeutics exploiting the immune response.