Genome-wide Association Study (GWAS) of Germline Copy Number Variations (CNVs) Reveal Genetic Risks of Prostate Cancer in Chinese population

Introduction: The associations between Prostate cancer (PCa) and germline copy number variations (CNVs) in genome-wide level based on Chinese population are unknown. The objective of this study was to identify possible PCa-risk associated CNV regions in Chinese population. Materials and Methods: We performed a genome-wide association study for CNV in 1,417 PCa cases and 1,008 controls in Chinese population. Results: 7 risk-associated CNVs were identified for PCa after association analyses (P <7.2×10(-6)). Another 34 CNVs were found to be potentially risk-associated CNVs (P<0.05). Among the total 41 CNVs, 27 CNVs were risk variations and the other 14 were found to be protective of PCa. 25 of the CNVs (19 duplications and 6 deletions) were located in gene regions while 16 CNVs (9 duplications and 7 deletions) were located in intergenic regions. We identified a higher burden of gaining PCa-risk CNVs and a lower frequency of protective CNVs in cases than controls. Bioinformatics analyses suggested that genes related to PCa risk-associated CNVs were significantly enriched in some biological processes, cellular components and molecular functions. Conclusion: These results provided additional information of genetic risks for PCa. Several CNV regions involved actionable genes that might be potential gene for target therapy. Additional validation and functional studies are warranted for these results.