Assessing the Role of Copy Number Variants in Prostate Cancer Risk and Progression Using a Novel Genomewide Screening Method.

摘要

Individual copy number variations in the genome may play a substantial role in influencing trait variation, yet due to technical limitations they have been understudied. We have performed the first genome-wide association of copy number variants and risk for prostate cancer in Mexican Americans. Our results from direct testing of CNVs are consistent with the growing consensus that there are not common genetic variants of large additive effects on prostate cancer predisposition, regardless of variant type. We found a highly protective rare deletion on 8q24 which is present in Mexican Americans but extremely rare in Caucasians. Due to the strong effect of this deletion, this discovery has implications for prostate cancer risk assessment and for understanding the etiology of prostate cancer. This variant warrants further study. We have also identified a rare 900 bp deletion in the PTEN gene to be associated with increased risk for prostate cancer and have provided confirmatory data that a rare heritable deletion on 2p24.3 is associated with prostate cancer risk in non-Hispanic Caucasians. These data support our hypothesis that heritable structural variation may affect risk for prostate cancer and/or its progression, but these variants are likely rare. Moreover, these variants may be unique to ethnic population and underscores the need to investigate genetic risk in multiple populations. As genes are identified from these studies, they may prove to be both useful biomarkers for early diagnosis and/or novel therapeutic targets for both prevention and treatment of prostate cancer.