Stella Koutros

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NCI, DCEG, OEEB

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PLCO (Learn more about this study)

2011-0039

Mar 9, 2011

KIR/HLA/MIR148A variation and risk of prostate cancer

Prostatitis, sexually transmitted infections, intake of anti-inflammatory drugs and antioxidants, have been suggested to contribute to prostate cancer risk through inflammatory processes. In addition, studies have shown that genetic variation and altered expression of genes involved in immune response processes play a role in the clinical course (progression) of prostate cancer. Natural killer (NK) cells are the first line of defense against viral infections and tumors. NK cell activity is controlled in part by interactions between killer immunoglobulin like receptors (KIR), which are expressed on the NK cells, and human leukocyte antigen (HLA) class I ligands expressed on all nucleated cells. Differential inhibition and activation of NK cells mediated by variation in these genes may influence tumor development and progression among malignancies involving a chronic inflammatory component, like prostate cancer. Recently allelic variation in HLA genes has been shown to result in their differential expression, which may also have an influence on risk of disease. Using high-resolution genotyping in a large population of PLCO prostate cancer cases (4,500) and controls (3,500), we propose to evaluate variation in regions that code for differential response to inflammatory signals and risk of total and aggressive prostate cancer. Findings from the proposed study could have a significant impact on our understanding of the role of inflammation in prostate cancer etiology.