Abstract 3048: Enhanced androgen signalling pathway increases the risk of prostate cancer through induction of TMPRSS2:ERG fusion

Clinical incidence and mortality rates of prostate cancer vary dramatically among different countries. In a recent study, we associated the difference in clinical incidence with certain somatic genomic alterations, including PTEN deletion and TMPRSS2:ERG fusion, which are found more commonly in Western but rarely in Chinese cancer samples (Mao et al, Cancer Res, 2010; 70:5207-12). TMPRSS2:ERG fusion, which is transcriptionally controlled by androgen receptor (AR), has been reported in more than 50% of prostate cancers. We investigated whether androgen level and AR activity, which varies between Chinese and Western men, could induce this fusion gene and consequently prostate cancer development. Since AR activity is inversely associated with its exon1 CAG repeats length, we determined the differences in repeat length between TMPRSS2:ERG fusion positive and negative UK samples and also between UK and China prostate cancer patients. We found significantly shorter CAG repeat lengths in the UK compared to Chinese cases (P