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

David V Conti; Kan Wang; Xin Sheng; Jeannette T Bensen; Dennis J Hazelett; Michael B Cook; Sue A Ingles; Rick A Kittles; Sara S Strom; Benjamin A Rybicki; Barbara Nemesure; William B Isaacs; Janet L Stanford; Wei Zheng; Maureen Sanderson; Esther M John; Jong Y Park; Jianfeng Xu; Victoria L Stevens; Sonja I Berndt; Chad D Huff; Zhaoming Wang; Edward D Yeboah; Yao Tettey; Richard B Biritwum; Andrew A Adjei; Evelyn Tay; Ann Truelove; Shelley Niwa; Thomas A Sellers; Kosj Yamoah; Adam B Murphy; Dana C Crawford; Susan M Gapstur; William S Bush; Melinda C Aldrich; Olivier Cussenot; Gyorgy Petrovics; Jennifer Cullen; Christine Neslund-Dudas; Mariana C Stern; Zsofia-Kote Jarai; Koveela Govindasami; Anand P Chokkalingam; Ann W Hsing; Phyllis J Goodman; Thomas Hoffmann; Bettina F Drake; Jennifer J Hu; Peter E Clark; Stephen K Van Den Eeden; Pascal Blanchet; Jay H Fowke; Graham Casey; Anselm J M Hennis; Ying Han; Alexander Lubwama; Ian M Thompson, Jr; Robin Leach; Douglas F Easton; Fredrick Schumacher; David J Van den Berg; Susan M Gundell; Alex Stram; Peggy Wan; Lucy Xia; Loreall C Pooler; James L Mohler; Elizabeth T H Fontham; Gary J Smith; Jack A Taylor; Shiv Srivastava; Rosalind A Eeles; John Carpten; Adam S Kibel; Luc Multigner; Marie-Elise Parent; Florence Menegaux; Geraldine Cancel-Tassin; Eric A Klein; Laurent Brureau; Daniel O Stram; Stephen Watya; Stephen J Chanock; John S Witte; William J Blot; Brian E Henderson; Christopher A Haiman

doi:10.1093/jnci/djx084

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

Journal article

Open access

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

David V Conti, Kan Wang, Xin Sheng, Jeannette T Bensen, Dennis J Hazelett, Michael B Cook, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, …

JNCI : Journal of the National Cancer Institute, Vol.109(8), p.djx084

2017-08-01

DOI: https://doi.org/10.1093/jnci/djx084

PMCID: PMC5448553

PMID: 29117387

Abstract

Genetic Predisposition to Disease

Genome-Wide Association Study

Gene Frequency

Humans

Male

Prostatic Neoplasms - ethnology

Genetic Loci

Case-Control Studies

Checkpoint Kinase 2 - genetics

Prostatic Neoplasms - genetics

Chromosomes, Human, Pair 13

Chromosomes, Human, Pair 22

Polymorphism, Single Nucleotide

African Continental Ancestry Group - genetics

Insulin Receptor Substrate Proteins - genetics

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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.455 Genome-Wide Association Studies
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry
Creators: David V Conti - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Kan Wang - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Xin Sheng - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Jeannette T Bensen - Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
Dennis J Hazelett - Bioinformatics and Computational Biology Research Center, Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
Michael B Cook - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Sue A Ingles - Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Rick A Kittles - University of Arizona College of Medicine and University of Arizona Cancer Center, Tucson, AZ
Sara S Strom - Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX
Benjamin A Rybicki - Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI
Barbara Nemesure - Department of Preventive Medicine, Stony Brook University, Stony Brook, NY
William B Isaacs - James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD
Janet L Stanford - Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
Wei Zheng - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN
Maureen Sanderson - Department of Family and Community Medicine, Meharry Medical College, Nashville, TN
Esther M John - Department of Health Research and Policy (Epidemiology), Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
Jong Y Park - Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL
Jianfeng Xu - Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL
Victoria L Stevens - Epidemiology Research Program, American Cancer Society, Atlanta, GA
Sonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
Chad D Huff - Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX
Zhaoming Wang - Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN
Edward D Yeboah - Korle Bu Teaching Hospital, Accra, Ghana
Yao Tettey - Korle Bu Teaching Hospital, Accra, Ghana
Richard B Biritwum - Korle Bu Teaching Hospital, Accra, Ghana
Andrew A Adjei - Korle Bu Teaching Hospital, Accra, Ghana
Evelyn Tay - Korle Bu Teaching Hospital, Accra, Ghana
Ann Truelove - Westat, Rockville, MD
Shelley Niwa - Westat, Rockville, MD
Thomas A Sellers - Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL
Kosj Yamoah - Department of Radiation Oncology and Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL
Adam B Murphy - Department of Urology, Northwestern University, Chicago, IL
Dana C Crawford - Institute for Computational Biology, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
Susan M Gapstur - Epidemiology Research Program, American Cancer Society, Atlanta, GA
William S Bush - Institute for Computational Biology, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
Melinda C Aldrich - Division of Epidemiology, Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, TN
Olivier Cussenot - CeRePP, GRC No. 5 ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Univ Paris 6, Paris, France
Gyorgy Petrovics - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD
Jennifer Cullen - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD
Christine Neslund-Dudas - Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI
Mariana C Stern - Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Zsofia-Kote Jarai - The Institute of Cancer Research, Sutton, London, UK
Koveela Govindasami - Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK
Anand P Chokkalingam - School of Public Health, University of California, Berkeley, Berkeley, CA
Ann W Hsing - Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
Phyllis J Goodman - SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA
Thomas Hoffmann - Department of Epidemiology and Biostatistics, University of California, San Francisco, CA
Bettina F Drake - Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO
Jennifer J Hu - Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL
Peter E Clark - Vanderbilt University Medical Center, Nashville, TN
Stephen K Van Den Eeden - Division of Research, Kaiser Permanente Northern California, Oakland, CA
Pascal Blanchet - French West Indies University, Pointe-à-Pitre, Guadeloupe, FWI
Jay H Fowke - Department of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN
Graham Casey - Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA
Anselm J M Hennis - Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados
Ying Han - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Alexander Lubwama - School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda
Ian M Thompson, Jr - Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX
Robin Leach - Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX
Douglas F Easton - Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
Fredrick Schumacher - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH
David J Van den Berg - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Susan M Gundell - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Alex Stram - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Peggy Wan - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Lucy Xia - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
Loreall C Pooler - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
James L Mohler - Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
Elizabeth T H Fontham - School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA
Gary J Smith - Department of Urology, Roswell Park Cancer Institute, Buffalo, NY
Jack A Taylor - Epigenetic and Stem Cell Biology Laboratory and Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC
Shiv Srivastava - Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD
Rosalind A Eeles - Royal Marsden NHS Foundation Trust, London, UK
John Carpten - Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA
Adam S Kibel - Washington University, St. Louis, MO
Luc Multigner - Inserm U1085 - IRSET, Rennes, France
Marie-Elise Parent - INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, University of Quebec, Laval, Quebec, Canada (MEP)
Florence Menegaux - Inserm, Team Cancer-Environment, Center for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, Villejuif, France
Geraldine Cancel-Tassin - CeRePP, GRC No. 5 ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Univ Paris 6, Paris, France
Eric A Klein - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH
Laurent Brureau - French West Indies University, Pointe-à-Pitre, Guadeloupe, FWI
Daniel O Stram - Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Stephen Watya - Uro Care, Kampala, Uganda
Stephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
John S Witte - Institute for Human Genetics, University of California, San Francisco, CA
William J Blot - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN
Brian E Henderson - Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Christopher A Haiman - Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.109(8), p.djx084
Publisher: United States
Grant note: R01 CA088164 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS K07 CA172294 / NCI NIH HHS G12 MD007586 / NIMHD NIH HHS U54 CA163069 / NCI NIH HHS P30 CA016086 / NCI NIH HHS UM1 CA182883 / NCI NIH HHS U01 CA086402 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Public Health Sciences Research
Language: English
Resource Type: Journal article
PMID: 29117387
PMCID: PMC5448553
Record Identifier: 991031560296102976