Abstract
Background: Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among African American men. The hereditary prostate cancer 1 gene (HPC1-1q24-25) was initially implicated as a PCa susceptibility locus in 1996, but was not replicated in the African American Hereditary Prostate Cancer (AAHPC) study, which recruited African American families with four or more affected family members (n=95 families). The objective of our study is to identify and confirm PCa genetic susceptibility loci in African Americans.
Methods: Short tandem repeat polymorphism (STR) scans implicated several loci, but no specific family had a logarithm of odds score higher than 1.8. We sought to refine implicated loci through single nucleotide polymorphism microarray. Therefore, we devised a prioritization scoring system where families with multiple affected and unaffected brothers within a likely onset age bracket scored the highest. After Illumina 660K microarray run, Bayesian prior likelihoods will be coupled with family based statistics to analyze the data in 6 families (n=32).
Results: Scoring criteria was effective at identifying families (n=31, 14 cases, 17 controls) most informative at identifying genes and SNPs associated PCa. A total of 51 SNPs in 13 genes were found to be associated with PCa Risk at the p<0.05 level including CTBP2 (4p16), HNF1B (17cen-q21.3), and PKHD1 (6p12.2).
Conclusions: This study is a first step in identifying PCa genes that warrant further follow-up in the rest of the AAHPC families.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A69.
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