Quantitative gene expression at the 8q24 prostate cancer risk locus

2008 
5055 Background: The 8q24 chromosome locus has emerged as a genetic risk factor for prostate cancer. How the locus exerts its effect, however, is currently unknown because the risk variants are situated in non-coding regions. One hypothesis is that the risk alleles influence expression of one or more genes in the region. We sought to define the transcriptional landscape at 8q24 and identify the gene(s) influenced by the risk polymorphisms. More generally, we provide an approach for following up risk alleles from genome wide scans. Methods: DNA and RNA were isolated from 124 individuals from the Dana-Farber Cancer Institute/Gelb Center cohort. The DNA was isolated from blood samples and genotyped for 6 single nucleotide polymorphisms (SNPs) shown to contribute independently to prostate cancer risk. RNA was isolated from histologically normal tissue from radical prostatectomy specimens. To comprehensively evaluate transcription, a Nimblegen tiling array was constructed spanning 5 megabases across 8q24 at 8 ...
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