Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Z Kote-Jarai; E J Saunders; D A Leongamornlert; M Tymrakiewicz; T Dadaev; S Jugurnauth-Little; H Ross-Adams; A A Al Olama; S Benlloch; S Halim; R Russel; A M Dunning; C Luccarini; J Dennis; D E Neal; F C Hamdy; J L Donovan; K Muir; G G Giles; G Severi; F Wiklund; H Gronberg; C A Haiman; F Schumacher; B E Henderson; L L Marchand; S Lindstrom; P Kraft; D J Hunter; S Gapstur; S Chanock; S I Berndt; D Albanes; G Andriole; J Schleutker; M Weischer; F Canzian; E Riboli; T J Key; R C Travis; D Campa; S A Ingles; E M John; R B Hayes; P Pharoah; K T Khaw; J L Stanford; E A Ostrander; L B Signorello; S N Thibodeau; D Schaid; C Maier; W Vogel; A S Kibel; C Cybulski; J Lubinski; L Cannon-Albright; H Brenner; J Y Park; R Kaneva; J Batra; A Spurdle; J A Clements; M R Teixeira; K Govindasami; M Guy; R A Wilkinson; E J Sawyer; A Morgan; E Dicks; C Baynes; D Conroy; S E Bojesen; R Kaaks; D Vincent; F Bacot; D C Tessier; D F Easton; R A Eeles

doi:10.1093/hmg/ddt086

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Z Kote-Jarai
, E J Saunders
, D A Leongamornlert
, M Tymrakiewicz
, T Dadaev
, S Jugurnauth-Little
, H Ross-Adams
, A A Al Olama
, S Benlloch
, S Halim
, R Russel
, A M Dunning
, C Luccarini
, J Dennis
, D E Neal
, F C Hamdy
, J L Donovan
, K Muir
, G G Giles
, G Severi

F Wiklund, H Gronberg, C A Haiman, F Schumacher, B E Henderson, L L Marchand, S Lindstrom, P Kraft, D J Hunter, S Gapstur, S Chanock, S I Berndt, D Albanes, G Andriole, J Schleutker, M Weischer, F Canzian, E Riboli, T J Key, R C Travis, D Campa, S A Ingles, E M John, R B Hayes, P Pharoah, K T Khaw, J L Stanford, E A Ostrander, L B Signorello, S N Thibodeau, D Schaid, C Maier, W Vogel, A S Kibel, C Cybulski, J Lubinski, L Cannon-Albright, H Brenner, J Y Park, R Kaneva, J Batra, A Spurdle, J A Clements, M R Teixeira, K Govindasami, M Guy, R A Wilkinson, E J Sawyer, A Morgan, E Dicks, C Baynes, D Conroy, S E Bojesen, R Kaaks, D Vincent, F Bacot, D C Tessier, D F Easton, R A Eeles

Research output: Contribution to journal › Article › peer-review

Abstract

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Original language	English
Journal	Hum Mol Genet
DOIs	https://doi.org/10.1093/hmg/ddt086
Publication status	Published - 2013

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SDG 3 Good Health and Well-being

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10.1093/hmg/ddt086

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Kote-Jarai, Z., Saunders, E. J., Leongamornlert, D. A., Tymrakiewicz, M., Dadaev, T., Jugurnauth-Little, S., Ross-Adams, H., Al Olama, A. A., Benlloch, S., Halim, S., Russel, R., Dunning, A. M., Luccarini, C., Dennis, J., Neal, D. E., Hamdy, F. C., Donovan, J. L., Muir, K., Giles, G. G., ... Eeles, R. A. (2013). Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Hum Mol Genet. https://doi.org/10.1093/hmg/ddt086

@article{c614e378116c4bd58d7b8948101db704,

title = "Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression",

abstract = "Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.",

author = "Z Kote-Jarai and Saunders, \{E J\} and Leongamornlert, \{D A\} and M Tymrakiewicz and T Dadaev and S Jugurnauth-Little and H Ross-Adams and \{Al Olama\}, \{A A\} and S Benlloch and S Halim and R Russel and Dunning, \{A M\} and C Luccarini and J Dennis and Neal, \{D E\} and Hamdy, \{F C\} and Donovan, \{J L\} and K Muir and Giles, \{G G\} and G Severi and F Wiklund and H Gronberg and Haiman, \{C A\} and F Schumacher and Henderson, \{B E\} and Marchand, \{L L\} and S Lindstrom and P Kraft and Hunter, \{D J\} and S Gapstur and S Chanock and Berndt, \{S I\} and D Albanes and G Andriole and J Schleutker and M Weischer and F Canzian and E Riboli and Key, \{T J\} and Travis, \{R C\} and D Campa and Ingles, \{S A\} and John, \{E M\} and Hayes, \{R B\} and P Pharoah and Khaw, \{K T\} and Stanford, \{J L\} and Ostrander, \{E A\} and Signorello, \{L B\} and Thibodeau, \{S N\} and D Schaid and C Maier and W Vogel and Kibel, \{A S\} and C Cybulski and J Lubinski and L Cannon-Albright and H Brenner and Park, \{J Y\} and R Kaneva and J Batra and A Spurdle and Clements, \{J A\} and Teixeira, \{M R\} and K Govindasami and M Guy and Wilkinson, \{R A\} and Sawyer, \{E J\} and A Morgan and E Dicks and C Baynes and D Conroy and Bojesen, \{S E\} and R Kaaks and D Vincent and F Bacot and Tessier, \{D C\} and Easton, \{D F\} and Eeles, \{R A\}",

note = "Kote-Jarai, Zsofia Saunders, Edward J Leongamornlert, Daniel A Tymrakiewicz, Malgorzata Dadaev, Tokhir Jugurnauth-Little, Sarah Ross-Adams, Helen Al Olama, Ali Amin Benlloch, Sara Halim, Silvia Russel, Roslin Dunning, Alison M Luccarini, Craig Dennis, Joe Neal, David E Hamdy, Freddie C Donovan, Jenny L Muir, Ken Giles, Graham G Severi, Gianluca Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A Schumacher, Fredrick Henderson, Brian E Marchand, Loic Le Lindstrom, Sara Kraft, Peter Hunter, David J Gapstur, Susan Chanock, Stephen Berndt, Sonja I Albanes, Demetrius Andriole, Gerald Schleutker, Johanna Weischer, Maren Canzian, Federico Riboli, Elio Key, Tim J Travis, Ruth C Campa, Daniele Ingles, Sue A John, Esther M Hayes, Richard B Pharoah, Paul Khaw, Kay-Tee Stanford, Janet L Ostrander, Elaine A Signorello, Lisa B Thibodeau, Stephen N Schaid, Dan Maier, Christiane Vogel, Walther Kibel, Adam S Cybulski, Cezary Lubinski, Jan Cannon-Albright, Lisa Brenner, Hermann Park, Jong Y Kaneva, Radka Batra, Jyotsna Spurdle, Amanda Clements, Judith A Teixeira, Manuel R Govindasami, Koveela Guy, Michelle Wilkinson, Rosemary A Sawyer, Emma J Morgan, Angela Dicks, Ed Baynes, Caroline Conroy, Don Bojesen, Stig E Kaaks, Rudolf Vincent, Daniel Bacot, Francois Tessier, Daniel C COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology The UK ProtecT Study Collaborators The PRACTICAL Consortium Easton, Douglas F Eeles, Rosalind A Human molecular genetics Hum Mol Genet. 2013 Mar 27.",

year = "2013",

doi = "10.1093/hmg/ddt086",

language = "English",

journal = "Hum Mol Genet",

issn = "0964-6906",

publisher = "Oxford University Press",

}

Kote-Jarai, Z, Saunders, EJ, Leongamornlert, DA, Tymrakiewicz, M, Dadaev, T, Jugurnauth-Little, S, Ross-Adams, H, Al Olama, AA, Benlloch, S, Halim, S, Russel, R, Dunning, AM, Luccarini, C, Dennis, J, Neal, DE, Hamdy, FC, Donovan, JL, Muir, K, Giles, GG, Severi, G, Wiklund, F, Gronberg, H, Haiman, CA, Schumacher, F, Henderson, BE, Marchand, LL, Lindstrom, S, Kraft, P, Hunter, DJ, Gapstur, S, Chanock, S, Berndt, SI, Albanes, D, Andriole, G, Schleutker, J, Weischer, M, Canzian, F, Riboli, E, Key, TJ, Travis, RC, Campa, D, Ingles, SA, John, EM, Hayes, RB, Pharoah, P, Khaw, KT, Stanford, JL, Ostrander, EA, Signorello, LB, Thibodeau, SN, Schaid, D, Maier, C, Vogel, W, Kibel, AS, Cybulski, C, Lubinski, J, Cannon-Albright, L, Brenner, H, Park, JY, Kaneva, R, Batra, J, Spurdle, A, Clements, JA, Teixeira, MR, Govindasami, K, Guy, M, Wilkinson, RA, Sawyer, EJ, Morgan, A, Dicks, E, Baynes, C, Conroy, D, Bojesen, SE, Kaaks, R, Vincent, D, Bacot, F, Tessier, DC, Easton, DF & Eeles, RA 2013, 'Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression', Hum Mol Genet. https://doi.org/10.1093/hmg/ddt086

TY - JOUR

T1 - Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

AU - Kote-Jarai, Z

AU - Saunders, E J

AU - Leongamornlert, D A

AU - Tymrakiewicz, M

AU - Dadaev, T

AU - Jugurnauth-Little, S

AU - Ross-Adams, H

AU - Al Olama, A A

AU - Benlloch, S

AU - Halim, S

AU - Russel, R

AU - Dunning, A M

AU - Luccarini, C

AU - Dennis, J

AU - Neal, D E

AU - Hamdy, F C

AU - Donovan, J L

AU - Muir, K

AU - Giles, G G

AU - Severi, G

AU - Wiklund, F

AU - Gronberg, H

AU - Haiman, C A

AU - Schumacher, F

AU - Henderson, B E

AU - Marchand, L L

AU - Lindstrom, S

AU - Kraft, P

AU - Hunter, D J

AU - Gapstur, S

AU - Chanock, S

AU - Berndt, S I

AU - Albanes, D

AU - Andriole, G

AU - Schleutker, J

AU - Weischer, M

AU - Canzian, F

AU - Riboli, E

AU - Key, T J

AU - Travis, R C

AU - Campa, D

AU - Ingles, S A

AU - John, E M

AU - Hayes, R B

AU - Pharoah, P

AU - Khaw, K T

AU - Stanford, J L

AU - Ostrander, E A

AU - Signorello, L B

AU - Thibodeau, S N

AU - Schaid, D

AU - Maier, C

AU - Vogel, W

AU - Kibel, A S

AU - Cybulski, C

AU - Lubinski, J

AU - Cannon-Albright, L

AU - Brenner, H

AU - Park, J Y

AU - Kaneva, R

AU - Batra, J

AU - Spurdle, A

AU - Clements, J A

AU - Teixeira, M R

AU - Govindasami, K

AU - Guy, M

AU - Wilkinson, R A

AU - Sawyer, E J

AU - Morgan, A

AU - Dicks, E

AU - Baynes, C

AU - Conroy, D

AU - Bojesen, S E

AU - Kaaks, R

AU - Vincent, D

AU - Bacot, F

AU - Tessier, D C

AU - Easton, D F

AU - Eeles, R A

N1 - Kote-Jarai, Zsofia Saunders, Edward J Leongamornlert, Daniel A Tymrakiewicz, Malgorzata Dadaev, Tokhir Jugurnauth-Little, Sarah Ross-Adams, Helen Al Olama, Ali Amin Benlloch, Sara Halim, Silvia Russel, Roslin Dunning, Alison M Luccarini, Craig Dennis, Joe Neal, David E Hamdy, Freddie C Donovan, Jenny L Muir, Ken Giles, Graham G Severi, Gianluca Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A Schumacher, Fredrick Henderson, Brian E Marchand, Loic Le Lindstrom, Sara Kraft, Peter Hunter, David J Gapstur, Susan Chanock, Stephen Berndt, Sonja I Albanes, Demetrius Andriole, Gerald Schleutker, Johanna Weischer, Maren Canzian, Federico Riboli, Elio Key, Tim J Travis, Ruth C Campa, Daniele Ingles, Sue A John, Esther M Hayes, Richard B Pharoah, Paul Khaw, Kay-Tee Stanford, Janet L Ostrander, Elaine A Signorello, Lisa B Thibodeau, Stephen N Schaid, Dan Maier, Christiane Vogel, Walther Kibel, Adam S Cybulski, Cezary Lubinski, Jan Cannon-Albright, Lisa Brenner, Hermann Park, Jong Y Kaneva, Radka Batra, Jyotsna Spurdle, Amanda Clements, Judith A Teixeira, Manuel R Govindasami, Koveela Guy, Michelle Wilkinson, Rosemary A Sawyer, Emma J Morgan, Angela Dicks, Ed Baynes, Caroline Conroy, Don Bojesen, Stig E Kaaks, Rudolf Vincent, Daniel Bacot, Francois Tessier, Daniel C COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology The UK ProtecT Study Collaborators The PRACTICAL Consortium Easton, Douglas F Eeles, Rosalind A Human molecular genetics Hum Mol Genet. 2013 Mar 27.

PY - 2013

Y1 - 2013

N2 - Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

AB - Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

U2 - 10.1093/hmg/ddt086

DO - 10.1093/hmg/ddt086

M3 - Article

SN - 0964-6906

JO - Hum Mol Genet

JF - Hum Mol Genet

ER -

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

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