Evaluation of the 8q24 prostate cancer risk locus and MYC expression.
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.
Pomerantz
Mark M
MM
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Beckwith
Christine A
CA
Regan
Meredith M
MM
Wyman
Stacia K
SK
Petrovics
Gyorgy
G
Chen
Yongmei
Y
Hawksworth
Dorota J
DJ
Schumacher
Fredrick R
FR
Mucci
Lorelei
L
Penney
Kathryn L
KL
Stampfer
Meir J
MJ
Chan
Jennifer A
JA
Ardlie
Kristin G
KG
Fritz
Brian R
BR
Parkin
Rachael K
RK
Lin
Daniel W
DW
Dyke
Michelle
M
Herman
Paula
P
Lee
Steve
S
Oh
William K
WK
Kantoff
Philip W
PW
Tewari
Muneesh
M
McLeod
David G
DG
Srivastava
Shiv
S
Freedman
Matthew L
ML
D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm / Q000235:genetics; D012306:Risk; D014158:Transcription, Genetic
D017931:DNA Primers; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm