Molecular Epidemiology of Prostate Cancer

In Austria prostate cancer is the most common malignancy in men and ranking second in cancer mortality exceeded only by lung cancer as observed in other industrialized countries. Despite the high prevalence of prostate cancer little is known about its etiology. The accepted risk factors are advanced age, ethnicity with highest incidence rates in Africans and genetic factors.
The identification of biomarkers indicating prostate cancer aggressiveness and progression at the time of diagnosis is of clinical importance, because prostate cancer often progresses slowly. These patients may be candidates for watchful waiting rather than surgical treatment. The development of a polygenic model for prostate cancer, especially aggressive prostate cancer, identified by genome-wide studies (GWAS), will allow the identification of individuals with high risk, resulting in better preventive, diagnostic and therapeutic strategies.

1. Genome-wide association study (GWAS) of PC

To identify new and to confirm known prostate cancer susceptibility loci, we have performed a GWAS from our DNA bank using the genome-wide human SNP array 6.0 ® (Affymetrix). This SNP array contains single nucleotide polymorphisms (SNPs) as well as probes for the detection of copy number variations (CNV).

2. Integrated copy-number and gene expression analysis

To discover novel candidate genes for PC prognosis and progression, we profiled gene expression and DNA copy number alterations using Affymetrix GeneChip® technology in tumor cells from prostate cancer patients and benign prostate gland cells from patients with benign prostatic hyperplasia. Laser capture microdissection was used to gain the cell populations of interest as pure as possible. We also integrated the two datasets, as genes whose varied expression is due to a chromosomal alteration, may suggest a causal implication of these genes in the disease.