184 Background: Prostate cancer shows a wide variation in the clinical incidence and mortality rates of different geographical regions. While it is the most common male cancer in Western countries, it is much less frequent in Asian countries. We investigated genomic changes in prostate cancers from UK and China using microarrays to determine the genetic similarities and differences as well as the underlying mechanisms. Methods: We determined genome-wide genomic alterations using Affymetrix SNP array 6.0, and evaluated data using fluorescence in situ hybridisation (FISH) and immunohistochemistry. In addition, we assess androgen induced TMPRSS2 and ERG co-localization and fusion. Microsatellite analysis was used for AR CAG repeat polymorphism in UK and Chinese population. Results: Genome-wide analysis of 32 UK and 39 Chinese samples revealed that losses of 21q22 (leading to TMPRSS2:ERG fusion) and 10q23.3 (PTEN) were at much higher frequency in Western than Chinese prostate cancers. Using FISH analysis of 160 UK and 143 Chinese samples, we showed that PTEN deletion and ERG rearrangements were at a significantly higher frequency in samples from UK than China (p<0.001 for both). We found that PTEN and ERG protein were also differentially expressed (p<0.001) in the two populations. Investigating this further, we induced TMPRSS2 and ERG gene proximity and TMPRSS2:ERG fusion in two immortalised prostate epithelial cell lines by exposure to high dose of androgen. This androgen treatment did not cause increased global DNA damage but was associated with low expression of PIWIL1, which is involved in repairing double-strand breaks. Overexpression of PIWIL1 by transfection inhibited androgen induced TMPRSS2:ERG fusion. We found that AR CAG repeat lengths, which associated with AR activity, are significantly shorter in the UK than Chinese patients (p<0.05). Conclusions: We revealed genomic differences in prostate cancer comparing the high-risk (Western) and low-risk (Chinese) populations. We further demonstrated that TMPRSS2:ERG fusion can be induced by androgen. The difference of CAG repeat length between the two populations are potentially associated with TMPRSS2:ERG fusion positive prostate cancers.