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J Natl Cancer Inst. 2017 Aug 1;109(8). doi: 10.1093/jnci/djx084.

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.

Author information

1
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
2
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
3
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
4
Bioinformatics and Computational Biology Research Center, Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA.
5
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
6
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
7
University of Arizona College of Medicine and University of Arizona Cancer Center, Tucson, AZ.
8
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX.
9
Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI.
10
Department of Preventive Medicine, Stony Brook University, Stony Brook, NY.
11
James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD.
12
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
13
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
14
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN.
15
Department of Family and Community Medicine, Meharry Medical College, Nashville, TN.
16
California Prevention Institute of California, Fremont, CA.
17
Department of Health Research and Policy (Epidemiology), Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.
18
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL.
19
Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL.
20
Epidemiology Research Program, American Cancer Society, Atlanta, GA.
21
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN.
22
University of Ghana Medical School, Accra, Ghana.
23
Korle Bu Teaching Hospital, Accra, Ghana.
24
Westat, Rockville, MD.
25
Department of Radiation Oncology and Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL.
26
Department of Urology, Northwestern University, Chicago, IL.
27
Institute for Computational Biology, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.
28
Division of Epidemiology, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN.
29
CeRePP, GRC No. 5 ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Univ Paris 6, Paris, France.
30
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD.
31
The Institute of Cancer Research, Sutton, London, UK.
32
Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK.
33
School of Public Health, University of California, Berkeley, Berkeley, CA.
34
Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.
35
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
36
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
37
Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO.
38
Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL.
39
Vanderbilt University Medical Center, Nashville, TN.
40
Division of Research, Kaiser Permanente Northern California, Oakland, CA.
41
University Hospital of Pointe-à-Pitre, Guadeloupe.
42
FWI and Inserm U1085-IRSET, Rennes, France.
43
French West Indies University, Pointe-à-Pitre, Guadeloupe, FWI.
44
Department of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN.
45
Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
46
Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados.
47
School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda.
48
Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX.
49
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
50
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.
51
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY.
52
School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA.
53
Epigenetic and Stem Cell Biology Laboratory and Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
54
Royal Marsden NHS Foundation Trust, London, UK.
55
Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA.
56
Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA.
57
Washington University, St. Louis, MO.
58
Inserm U1085 - IRSET, Rennes, France.
59
INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, University of Quebec, Laval, Quebec, Canada (MEP).
60
Inserm, Team Cancer-Environment, Center for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, Villejuif, France.
61
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
62
Uro Care, Kampala, Uganda.
63
Institute for Human Genetics, University of California, San Francisco, CA.

Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

PMID:
29117387
PMCID:
PMC5448553
DOI:
10.1093/jnci/djx084
[Indexed for MEDLINE]
Free PMC Article

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