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

被引：88

作者：

Pomerantz, Mark M. ^{[1
]}

Beckwith, Christine A. ^{[1
]}

Regan, Meredith M. ^{[2
]}

Wyman, Stacia K. ^{[4
]}

Petrovics, Gyorgy ^{[9
]}

Chen, Yongmei ^{[9
]}

Hawksworth, Dorota J. ^{[9
]}

Schumacher, Fredrick R. ^{[3
,6
]}

Mucci, Lorelei ^{[3
,6
]}

Penney, Kathryn L. ^{[3
]}

Stampfer, Meir J. ^{[3
,10
,11
,12
]}

Chan, Jennifer A. ^{[10
,11
,12
]}

Ardlie, Kristin G. ^{[13
]}

Fritz, Brian R. ^{[4
]}

Parkin, Rachael K. ^{[4
]}

Lin, Daniel W. ^{[5
,7
,8
]}

Dyke, Michelle ^{[1
]}

Herman, Paula ^{[1
]}

Lee, Steve ^{[1
]}

Oh, William K. ^{[1
]}

Kantoff, Philip W. ^{[1
]}

Tewari, Muneesh ^{[4
,6
]}

McLeod, David G. ^{[9
]}

Srivastava, Shiv ^{[9
]}

Freedman, Matthew L. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[4] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA USA

[5] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA

[6] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA

[7] Univ Washington, Dept Urol, Seattle, WA 98195 USA

[8] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA

[9] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Rockville, MD USA

[10] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada

[11] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada

[12] Univ Calgary, Dept Oncol, Calgary, AB, Canada

[13] Broad Inst Harvard & MIT, Cambridge, MA USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 13期

关键词：

GENOME-WIDE ASSOCIATION; CHROMOSOME; 8Q24; BREAST-CANCER; SUSCEPTIBILITY; VARIANT; GENE; OVEREXPRESSION; IDENTIFICATION; CELLS; TUMOR;

D O I：

10.1158/0008-5472.CAN-09-0387

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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]

引用

页码：5568 / 5574

页数：7

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