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The incidence and mortality rates of prostate cancer vary substantially among different geographic areas and ethnic groups.In order to effectively control prostate cancer, contributions of genetic variations among humans to the detection, diagnosis, and treatment response need to be better characterized.To test the hypothesis that prostate cancer biomarkers may be influenced by genetic variations, we first conducted genome-wide expression studies in prostate cancer patients from ethnically diverse populations.Both prostate tumors and tumor-associated normal tissues exhibited vastly different expression phenotypes according to geographic origin.Of importance, many putative prostate tumor markers that are only specific to one population were identified.While these differences are typically interpreted as a reflection of potentially different disease etiology and tumor microenvironment, we present two striking cases to illustrate the direct and one-on-one impact of germline copy number variations as well as single nucleotide differences on tumor specific expression phenotypes.The demonstration of genetic contribution to population-specific prostate cancer markers highlight the need to conduct biomarker studies in multiple ethnically diverse populations.Such emphasis, if implemented, will provide effective means to address the problem of cancer disparity.