Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression Export

@article{citeulike:5034499, abstract = {Polymorphisms at 8q24 are robustly associated with prostate cancer risk. The risk variants are located in nonprotein coding regions and their mechanism has not been fully elucidated. To further dissect the function of this locus, we tested two hypotheses: (a) unannotated microRNAs (miRNA) are transcribed in the region, and (b) this region is a cis-acting enhancer. Using next generation sequencing, 8q24 risk regions were interrogated for known and novel miRNAs in histologically normal radical prostatectomy tissue. We also evaluated the association between the risk variants and transcript levels of multiple genes, focusing on the proto-oncogene, MYC. RNA expression was measured in histologically normal and tumor tissue from 280 prostatectomy specimens (from 234 European American and 46 African American patients), and paired germline DNA from each individual was genotyped for six 8q24 risk single nucleotide polymorphisms. No evidence was found for significant miRNA transcription within 8q24 prostate cancer risk loci. Likewise, no convincing association between RNA expression and risk allele status was detected in either histologically normal or tumor tissue. To our knowledge, this is one of the first and largest studies to directly assess miRNA in this region and to systematically measure MYC expression levels in prostate tissue in relation to inherited risk variants. These data will help to direct the future study of this risk locus. [Cancer Res 2009;69(13):5568-74] 10.1158/0008-5472.CAN-09-0387}, author = {Pomerantz, Mark M. and Beckwith, Christine A. and Regan, Meredith M. and Wyman, Stacia K. and Petrovics, Gyorgy and Chen, Yongmei and Hawksworth, Dorota J. and Schumacher, Fredrick R. and Mucci, Lorelei and Penney, Kathryn L. and Stampfer, Meir J. and Chan, Jennifer A. and Ardlie, Kristin G. and Fritz, Brian R. and Parkin, Rachael K. and Lin, Daniel W. and Dyke, Michelle and Herman, Paula and Lee, Steve and Oh, William K. and Kantoff, Philip W. and Tewari, Muneesh and Mcleod, David G. and Srivastava, Shiv and Freedman, Matthew L.}, citeulike-article-id = {5034499}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-09-0387}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19549893}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19549893}, doi = {10.1158/0008-5472.CAN-09-0387}, journal = {Cancer Res}, keywords = {8q24, myc, prostate}, month = {June}, pages = {0008-5472.CAN-09-0387+}, posted-at = {2009-07-01 17:15:28}, priority = {2}, title = {Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-09-0387}, year = {2009} }

TY - JOUR ID - citeulike:5034499 L3 - citeulike-article-id:5034499 N2 - Polymorphisms at 8q24 are robustly associated with prostate cancer risk. The risk variants are located in nonprotein coding regions and their mechanism has not been fully elucidated. To further dissect the function of this locus, we tested two hypotheses: (a) unannotated microRNAs (miRNA) are transcribed in the region, and (b) this region is a cis-acting enhancer. Using next generation sequencing, 8q24 risk regions were interrogated for known and novel miRNAs in histologically normal radical prostatectomy tissue. We also evaluated the association between the risk variants and transcript levels of multiple genes, focusing on the proto-oncogene, MYC. RNA expression was measured in histologically normal and tumor tissue from 280 prostatectomy specimens (from 234 European American and 46 African American patients), and paired germline DNA from each individual was genotyped for six 8q24 risk single nucleotide polymorphisms. No evidence was found for significant miRNA transcription within 8q24 prostate cancer risk loci. Likewise, no convincing association between RNA expression and risk allele status was detected in either histologically normal or tumor tissue. To our knowledge, this is one of the first and largest studies to directly assess miRNA in this region and to systematically measure MYC expression levels in prostate tissue in relation to inherited risk variants. These data will help to direct the future study of this risk locus. [Cancer Res 2009;69(13):5568-74] 10.1158/0008-5472.CAN-09-0387 JF - Cancer Res TI - Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression SP - 0008-5472.CAN-09-0387 KW - 8q24 KW - myc KW - prostate AU - Pomerantz, Mark AU - Beckwith, Christine AU - Regan, Meredith AU - Wyman, Stacia AU - Petrovics, Gyorgy AU - Chen, Yongmei AU - Hawksworth, Dorota AU - Schumacher, Fredrick AU - Mucci, Lorelei AU - Penney, Kathryn AU - Stampfer, Meir AU - Chan, Jennifer AU - Ardlie, Kristin AU - Fritz, Brian AU - Parkin, Rachael AU - Lin, Daniel AU - Dyke, Michelle AU - Herman, Paula AU - Lee, Steve AU - Oh, William AU - Kantoff, Philip AU - Tewari, Muneesh AU - Mcleod, David AU - Srivastava, Shiv AU - Freedman, Matthew PY - 2009/06/23/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-09-0387 ER -