Identifying Genes for Prostate Cancer Risk


For men in the United States, prostate cancer is the most frequent of all cancers and the second most frequent for deaths due to cancer. Although prostate cancer can be caused by various factors, including screening methods, diet and health-related behaviors, clinical practice patterns, and environmental risk factors, there is also significant research that points to genetics.

Multiple genome-wide association studies (GWAS) have been performed recently, which have yielded many single-nucleotide polymorphisms (SNPs)  However, these studies present several key problems, including:

  1. The target gene for the risk SNP (or causal SNP) is most often unknown
  2. The causal SNP is unknown (most likely in linkage disequilibrium with the measured risk SNP)
  3. The functional consequence of the causal SNP is unknown

A frequently used strategy to address these problems involves the use of gene expression. Loci that control the expression level of individual mRNA transcripts, known as expression quantitative trait loci (eQTL), can be globally identified by comparing genome-wide SNP and genome-wide mRNA expression on a common set of samples.

Steven Thibodeau, Ph.D.

Mayo Clinic researchers, first author Steven Thibodeau, Ph.D., established and utilized a normal prostate tissue-specific eQTL data set to target and analyze the association of previously reported prostate cancer-risk SNPs and their SNPs with gene expression levels. The goal of the study, published in Nature Communicationswas to identify candidate target genes for each of the prostate cancer-risk SNPs and to fine map the eQTL signal with a dense set of SNPs for each of the target genes identified.

Of the 100 prostate cancer-risk intervals studied, 51 demonstrated a significant eQTL signal and these are associated with 88 target genes. These genes can now be prioritized for future study as candidate prostate cancer susceptibility genes. However, additional studies will be needed to identify those genes among the 88 that are truly involved in prostate cancer risk and to define their mechanism of action.


Kelley Schreiber

Kelley Schreiber is a Marketing Channel Manager at Mayo Medical Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her new kitten, and exploring new foods.