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J Natl Cancer Inst. 2016 Jan 27;108(7). doi: 10.1093/jnci/djv431. Print 2016 Jul.

Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.

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1
Affiliations of authors: Department of Preventive Medicine (YH, KAR, DJH, SAI, FRS, GC, LCP, XS, GAC, DOS, DVC, BEH, CAH) and Department of Urology (GAC), Keck School of Medicine, and Norris Comprehensive Cancer Center (SAI, FRS, GC, GAC, DOS, DVC, BEH, CAH), University of Southern California , Los Angeles, CA ; University of Arizona College of Medicine and University of Arizona Cancer Center , Tucson, AZ (RAK); Department of Epidemiology (SSS) and Department of Urology (CAP), University of Texas M. D. Anderson Cancer Center , Houston, TX ; Department of Public Health Sciences (BAR) and Department of Public Health Sciences (CND), Henry Ford Hospital , Detroit, MI ; Department of Preventive Medicine, Stony Brook University , Stony Brook, NY (BN, MCL, SYW, AJMH); James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution , Baltimore, MD (WBI); Division of Public Health Sciences (JLS, SK) and SWOG Statistical Center (PJG), Fred Hutchinson Cancer Research Center , Seattle, WA ; Department of Epidemiology, School of Public Health, University of Washington , Seattle, WA (JLS); Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine , Nashville, TN (WZ, WJB); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD (SIB, ZW, MBC, SJC); Cancer Genomics Research Laboratory, NCI-DCEG, SAIC-Frederick Inc. , Frederick, MD (ZW); Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem , Evanston, IL (JX); Department of Genetics (NR, DR, AT, AA, DQ, SM) and Howard Hughes Medical Institute (DR, SM), Harvard Medical School, Harvard University , Boston, MA ; Broad Institute of MIT and Harvard , Cambridge, MA (NR, DR, AT, AA, DQ, SM); Department of Pathology and Laboratory Medicine and Department of Human Genetics, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA (BP); Howard Hughes Medical Institute, Department of Medicine, School of Medicine, University of California , San Diego, San Diego, CA (DN, MGR, RSJ); Epidemiology Research Program, American Cancer Society , Atlanta, GA (SMG, VLS); Korle Bu Teaching Hospital , Accra , Ghana (EDY, YT, RBB, AAA, ET); University of Ghana Medical School , Accra , Ghana (EDY, YT, RBB, AAA, ET); Westat , Rockville, MD (AT, SN); School of Public Health, University of California , Berkeley, Berkeley, CA (APC); Cancer Prevention Institute of California , Fremont, CA (EMJ, AWH, LC); Stanford University School of Medicine and Stanford Cancer Institute , Palo Alto, CA (EMJ, AWH, LC); Department of Urology, Northwestern University , Chicago, IL (ABM); Department of Epidemiology, Harvard School of Public Health , Boston, MA (LBS, WJB); The Translational Genomics Research Institute , Phoenix, AZ (JC); Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies , Bridgetown, Barbados (AJMH); Glickman Urological & Kidney Institute, Cleveland Clinic , Cleveland, OH (EAK); Center for Cancer Genomics, Wake Forest School of Medicine , Winston-Salem, NC (SLZ); Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California , San Francisco, San Francisco, CA (JSW); School of Public Health, Makerere University College of Health Sciences , Kampala, Uganda (AL, SW); Uro Care , Kampala , Uganda (SW).

Abstract

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.

PMID:
26823525
PMCID:
PMC4948565
DOI:
10.1093/jnci/djv431
[Indexed for MEDLINE]
Free PMC Article

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