Use of eQTL Analysis for the Discovery of Target Genes Identified by GWAS

Prostate cancer (PC), the most-frequently diagnosed, solid tumor in men in the U.S., results in approximately 219,000 new cases and approximately 27,000 deaths per year. Although prostate cancer is likely to be the result of several factors, there is a great deal of research showing that genetics plays an important role in the development of this disease. That is, a variety of different genetic factors, when present, predispose men to more likely develop prostate cancer compared to others. Over the years, there have been a number of different types of molecular genetic studies directed at identifying these genetic factors. One of these, called Genome- Wide Association Study (GWAS), has emerged as one of the most widely-used approaches to identify genetic factors (in particular single nucleotide polymorphisms [SNPs]) that are associated with increased risk of developing disease, including prostate cancer. Based on these studies, a substantial number of these SNPs have now been found, and this number continues to grow. Additionally, these and other SNPs are being identified that predict the aggressiveness of the tumor for that patient. A significant problem with those SNPs identified by these studies, however, is that their function is almost completely unknown. Furthermore, the gene(s) affected by these SNPs are also unknown. The objective of this project is to first develop a laboratory-based resource, that is prostate tissue-specific, and then use that resource to discover which genes are most likely affected by those SNPs found to be important for prostate cancer. The long-term goal of this project is to acquire the ability to predict who will develop prostate cancer, and for those men that do develop disease, to have the ability to predict who will develop a more aggressive tumor, one that is life threatening. These long-term goals, however, are not possible unless we have a better understanding of the role and function of these genetic factors. In addition, having a better understanding of the genetic mechanisms for prostate cancer may lead to improved treatment strategies.