Prostate cancer (PC) is one of the most common malignancies of males in western countries. Although older age and African-American ancestry have long been recognized as important risk factors, there is much evidence that supports the notion that genetics plays a key role. This evidence comes from a wide range of studies, including familial aggregation, twin studies, family-based linkage studies, and molecular epidemiological studies of both rare and common polymorphisms of candidate genes.
However, the evidence also points towards a much more complex genetic basis than initially anticipated. As with other complex genetic disorders, familial PC is likely to be very heterogeneous, with the presence of multiple lower penetrant susceptibility genes.
Therefore, one of my research interests is to identify and characterize genetic susceptibility genes in hereditary PC and modifier genes in familial/sporadic PC. Currently, we are focused on chromosomal loci-specific association study using high throughput genotyping technologies. We have collected over 1500 DNA samples including familial cases, sporadic cases and population controls. This analysis will allow for fine mapping and potential identification of candidate genes.
Another research interest is to test the hypothesis that inherited variations in gene expression strongly influence tumor behavior and clinical outcome of PC. We believe that gene expression patterns measure not only expression of individual genes, but also function as surrogates for genetic markers to map the single-nucleotide polymorphisms that underlie both the gene-expression changes and tumor aggressiveness.
To achieve the goal, we are evaluating the inherited expression difference between patients with more aggressive cancer and patients with less aggressive cancer using gene expression profiling analysis. This study will help us identify genetic risk factors and markers responsible for aggressive behavior of PC. More importantly, characterization of inherited gene expression signature could point to targets for screening, preventive and therapeutic studies.