Genome-wide association study identifies new prostate cancer susceptibility loci

Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identif...

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Published in	Human molecular genetics Vol. 20; no. 19; pp. 3867 - 3875
Main Authors	Schumacher, Fredrick R., Berndt, Sonja I., Siddiq, Afshan, Jacobs, Kevin B., Wang, Zhaoming, Lindstrom, Sara, Stevens, Victoria L., Chen, Constance, Mondul, Alison M., Travis, Ruth C., Stram, Daniel O., Eeles, Rosalind A., Easton, Douglas F., Giles, Graham, Hopper, John L., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Muir, Kenneth, Al Olama, Ali Amin, Kote-Jarai, Zsofia, Guy, Michelle, Severi, Gianluca, Grönberg, Henrik, Isaacs, William B., Karlsson, Robert, Wiklund, Fredrik, Xu, Jianfeng, Allen, Naomi E., Andriole, Gerald L., Barricarte, Aurelio, Boeing, Heiner, Bas Bueno-de-Mesquita, H., Crawford, E. David, Diver, W. Ryan, Gonzalez, Carlos A., Gaziano, J. Michael, Giovannucci, Edward L., Johansson, Mattias, Le Marchand, Loic, Ma, Jing, Sieri, Sabina, Stattin, Pär, Stampfer, Meir J., Tjonneland, Anne, Vineis, Paolo, Virtamo, Jarmo, Vogel, Ulla, Weinstein, Stephanie J., Yeager, Meredith, Thun, Michael J., Kolonel, Laurence N., Henderson, Brian E., Albanes, Demetrius, Hayes, Richard B., Spencer Feigelson, Heather, Riboli, Elio, Hunter, David J., Chanock, Stephen J., Haiman, Christopher A., Kraft, Peter
Format	Journal Article
Language	English
Published	Oxford Oxford University Press 01.10.2011
Subjects	Association Studies Biological and medical sciences Case-Control Studies Cohort Studies Fundamental and applied biological sciences. Psychology Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Humans Male Medical sciences Molecular and cellular biology Nephrology. Urinary tract diseases Polymorphism, Single Nucleotide Prostatic Neoplasms - genetics Tumors of the urinary system Urinary tract. Prostate gland Urinary system disease Prostate disease Genetics Identification Malignant tumor Locus Male genital diseases Prostate cancer Cancer
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Abstract	Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10−8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10−9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
AbstractList	Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10−8). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10−9). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade greater than or equal to 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 10 super(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 10 super(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 × 10 −8 ). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 × 10 −9 ). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes. Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
Author	Tjonneland, Anne Mondul, Alison M. Diver, W. Ryan Vineis, Paolo Weinstein, Stephanie J. Hopper, John L. Kote-Jarai, Zsofia Neal, David E. Chanock, Stephen J. Travis, Ruth C. Giles, Graham Grönberg, Henrik Albanes, Demetrius Barricarte, Aurelio Schumacher, Fredrick R. Easton, Douglas F. Chen, Constance Jacobs, Kevin B. Bas Bueno-de-Mesquita, H. Hamdy, Freddie C. Riboli, Elio Wiklund, Fredrik Thun, Michael J. Guy, Michelle Yeager, Meredith Donovan, Jenny L. Stram, Daniel O. Kraft, Peter Sieri, Sabina Wang, Zhaoming Al Olama, Ali Amin Berndt, Sonja I. Gonzalez, Carlos A. Muir, Kenneth Spencer Feigelson, Heather Crawford, E. David Andriole, Gerald L. Stevens, Victoria L. Stattin, Pär Giovannucci, Edward L. Xu, Jianfeng Virtamo, Jarmo Vogel, Ulla Hayes, Richard B. Haiman, Christopher A. Lindstrom, Sara Karlsson, Robert Severi, Gianluca Allen, Naomi E. Johansson, Mattias Le Marchand, Loic Henderson, Brian E. Gaziano, J. Michael Ma, Jing Kolonel, Laurence N. Hunter, David J. Siddiq, Afshan Stampfer, Meir J. Isaacs, William B. Boeing, Heiner Eeles, Ros
AuthorAffiliation	39 Channing Laboratory , Boston, MA , USA 24 The Brady Urological Institute, Johns Hopkins Medical Institutions , Baltimore, MD , USA 4 MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London , London , UK 23 Department of Medical Epidemiology and Biostatistics , Karolinska Institutet , Stockholm , Sweden 2 Division of Cancer Epidemiology and Genetics , National Cancer Institute , Bethesda, MD , USA 25 Centers for Cancer Genomics and Center for Human Genomics , Wake Forest University School of Medicine , Winston-Salem, NC , USA 32 Division of Aging and 16 Department of Public Health 40 Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy 11 Cancer Epidemiology Unit 43 National Research Centre for the Working Environment , Copenhagen , Denmark 3 Department of Epidemiology and Biostatistics and 7 Program in Molecular and Genetic Epidemiology 13 Nuffield Department of Surgical Sciences , University of Oxford , Oxford , UK 15 C
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Copyright	The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2011 2015 INIST-CNRS
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Snippet	Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet...
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SubjectTerms	Association Studies Biological and medical sciences Case-Control Studies Cohort Studies Fundamental and applied biological sciences. Psychology Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Humans Male Medical sciences Molecular and cellular biology Nephrology. Urinary tract diseases Polymorphism, Single Nucleotide Prostatic Neoplasms - genetics Tumors of the urinary system Urinary tract. Prostate gland
Title	Genome-wide association study identifies new prostate cancer susceptibility loci
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