Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Zsofia Kote-Jarai; Ali Amin Al Olama; Graham G Giles; Gianluca Severi; Johanna Schleutker; Maren Weischer; Daniele Campa; Elio Riboli; Tim Key; Henrik Gronberg; David J Hunter; Peter Kraft; Michael J Thun; Sue Ingles; Stephen Chanock; Demetrius Albanes; Richard B Hayes; David E Neal; Freddie C Hamdy; Jenny L Donovan; Paul Pharoah; Fredrick Schumacher; Brian E Henderson; Janet L Stanford; Elaine A Ostrander; Karina Dalsgaard Sorensen; Thilo Dörk; Gerald Andriole; Joanne L Dickinson; Cezary Cybulski; Jan Lubinski; Amanda Spurdle; Judith A Clements; Suzanne Chambers; Joanne Aitken; R A Frank Gardiner; Stephen N Thibodeau; Dan Schaid; Esther M John; Christiane Maier; Walther Vogel; Kathleen A Cooney; Sung Jong Park; Lisa Cannon-Albright; Hermann Brenner; Ole Peter Klarskov; Børge G Nordestgaard; Andreas Røder; Anne Tybjærg-Hansen; Stig E Bojesen; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology

doi:10.1038/ng.882

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Zsofia Kote-Jarai, Ali Amin Al Olama, Graham G Giles, Gianluca Severi, Johanna Schleutker, Maren Weischer, Daniele Campa, Elio Riboli, Tim Key, Henrik Gronberg, David J Hunter, Peter Kraft, Michael J Thun, Sue Ingles, Stephen Chanock, Demetrius Albanes, Richard B Hayes, David E Neal, Freddie C Hamdy, Jenny L DonovanPaul Pharoah, Fredrick Schumacher, Brian E Henderson, Janet L Stanford, Elaine A Ostrander, Karina Dalsgaard Sorensen, Thilo Dörk, Gerald Andriole, Joanne L Dickinson, Cezary Cybulski, Jan Lubinski, Amanda Spurdle, Judith A Clements, Suzanne Chambers, Joanne Aitken, R A Frank Gardiner, Stephen N Thibodeau, Dan Schaid, Esther M John, Christiane Maier, Walther Vogel, Kathleen A Cooney, Sung Jong Park, Lisa Cannon-Albright, Hermann Brenner, Ole Peter Klarskov, Børge G Nordestgaard, Andreas Røder, Anne Tybjærg-Hansen, Stig E Bojesen, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology

249 Citations (Scopus)

Abstract

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.

Original language	English
Journal	Nature Genetics
Volume	43
Issue number	8
Pages (from-to)	785-91
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.882
Publication status	Published - 2011

Keywords

Adult
Aged
Aged, 80 and over
Case-Control Studies
Chromosomes, Human
Cohort Studies
Disease Susceptibility
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prostatic Neoplasms
Randomized Controlled Trials as Topic
Telomerase

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Kote-Jarai, Z., Olama, A. A. A., Giles, G. G., Severi, G., Schleutker, J., Weischer, M., Campa, D., Riboli, E., Key, T., Gronberg, H., Hunter, D. J., Kraft, P., Thun, M. J., Ingles, S., Chanock, S., Albanes, D., Hayes, R. B., Neal, D. E., Hamdy, F. C., ... UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology (2011). Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nature Genetics, 43(8), 785-91. https://doi.org/10.1038/ng.882

Kote-Jarai, Z, Olama, AAA, Giles, GG, Severi, G, Schleutker, J, Weischer, M, Campa, D, Riboli, E, Key, T, Gronberg, H, Hunter, DJ, Kraft, P, Thun, MJ, Ingles, S, Chanock, S, Albanes, D, Hayes, RB, Neal, DE, Hamdy, FC, Donovan, JL, Pharoah, P, Schumacher, F, Henderson, BE, Stanford, JL, Ostrander, EA, Sorensen, KD, Dörk, T, Andriole, G, Dickinson, JL, Cybulski, C, Lubinski, J, Spurdle, A, Clements, JA, Chambers, S, Aitken, J, Gardiner, RAF, Thibodeau, SN, Schaid, D, John, EM, Maier, C, Vogel, W, Cooney, KA, Park, SJ, Cannon-Albright, L, Brenner, H, Klarskov, OP, Nordestgaard, BG , Røder, A , Tybjærg-Hansen, A , Bojesen, SE & UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology 2011, 'Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study', Nature Genetics, vol. 43, no. 8, pp. 785-91. https://doi.org/10.1038/ng.882

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title = "Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study",

abstract = "Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.",

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author = "Zsofia Kote-Jarai and Olama, {Ali Amin Al} and Giles, {Graham G} and Gianluca Severi and Johanna Schleutker and Maren Weischer and Daniele Campa and Elio Riboli and Tim Key and Henrik Gronberg and Hunter, {David J} and Peter Kraft and Thun, {Michael J} and Sue Ingles and Stephen Chanock and Demetrius Albanes and Hayes, {Richard B} and Neal, {David E} and Hamdy, {Freddie C} and Donovan, {Jenny L} and Paul Pharoah and Fredrick Schumacher and Henderson, {Brian E} and Stanford, {Janet L} and Ostrander, {Elaine A} and Sorensen, {Karina Dalsgaard} and Thilo D{\"o}rk and Gerald Andriole and Dickinson, {Joanne L} and Cezary Cybulski and Jan Lubinski and Amanda Spurdle and Clements, {Judith A} and Suzanne Chambers and Joanne Aitken and Gardiner, {R A Frank} and Thibodeau, {Stephen N} and Dan Schaid and John, {Esther M} and Christiane Maier and Walther Vogel and Cooney, {Kathleen A} and Park, {Sung Jong} and Lisa Cannon-Albright and Hermann Brenner and Klarskov, {Ole Peter} and Nordestgaard, {B{\o}rge G} and Andreas R{\o}der and Anne Tybj{\ae}rg-Hansen and Bojesen, {Stig E} and {UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology}",

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AU - Kote-Jarai, Zsofia

AU - Olama, Ali Amin Al

AU - Giles, Graham G

AU - Severi, Gianluca

AU - Schleutker, Johanna

AU - Weischer, Maren

AU - Campa, Daniele

AU - Riboli, Elio

AU - Key, Tim

AU - Gronberg, Henrik

AU - Hunter, David J

AU - Kraft, Peter

AU - Thun, Michael J

AU - Ingles, Sue

AU - Chanock, Stephen

AU - Albanes, Demetrius

AU - Hayes, Richard B

AU - Neal, David E

AU - Hamdy, Freddie C

AU - Donovan, Jenny L

AU - Pharoah, Paul

AU - Schumacher, Fredrick

AU - Henderson, Brian E

AU - Stanford, Janet L

AU - Ostrander, Elaine A

AU - Sorensen, Karina Dalsgaard

AU - Dörk, Thilo

AU - Andriole, Gerald

AU - Dickinson, Joanne L

AU - Cybulski, Cezary

AU - Lubinski, Jan

AU - Spurdle, Amanda

AU - Clements, Judith A

AU - Chambers, Suzanne

AU - Aitken, Joanne

AU - Gardiner, R A Frank

AU - Thibodeau, Stephen N

AU - Schaid, Dan

AU - John, Esther M

AU - Maier, Christiane

AU - Vogel, Walther

AU - Cooney, Kathleen A

AU - Park, Sung Jong

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Klarskov, Ole Peter

AU - Nordestgaard, Børge G

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AU - Tybjærg-Hansen, Anne

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N2 - Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.

AB - Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Case-Control Studies

KW - Chromosomes, Human

KW - Cohort Studies

KW - Disease Susceptibility

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Prostatic Neoplasms

KW - Randomized Controlled Trials as Topic

KW - Telomerase

U2 - 10.1038/ng.882

DO - 10.1038/ng.882

M3 - Journal article

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SN - 1061-4036

VL - 43

SP - 785

EP - 791

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Abstract

Keywords

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