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

Zsofia Kote-Jarai, Edward J. Saunders, Daniel A. Leongamornlert, Malgorzata Tymrakiewicz, Tokhir Dadaev, Sarah Jugurn-Little, Helen Ross-Adams, Ali Amin Al Olama, Sara Benlloch, Silvia Halim, Roslin Russel, Alison M. Dunning, Craig Luccarini, Joe Dennis, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ken Muir, Graham G. Giles, Gianluca SeveriFredrik Wiklund, Henrik Gronberg, Christopher A. Haiman, Fredrick Schumacher, Brian E. Henderson, Loic Le Marchand, Sara Lindstrom, Peter Kraft, David J. Hunter, Susan Gapstur, Stephen Chanock, Sonja I. Berndt, Demetrius Albanes, Gerald Andriole, Johanna Schleutker, Maren Weischer, Federico Canzian, Elio Riboli, Tim J. Key, Ruth C. Travis, Daniele Campa, Sue A. Ingles, Esther M. John, Richard B. Hayes, Paul Pharoah, Kay Tee Khaw, Janet L. Stanford, Elaine A. Ostrander, Lisa B. Signorello, Stephen N Thibodeau, Daniel J Schaid, Christiane Maier, Walther Vogel, Adam S. Kibel, Cezary Cybulski, Jan Lubinski, Lisa Cannon-Albright, Hermann Brenner, Jong Y. Park, Radka Kaneva, Jyotsna Batra, Amanda Spurdle, Judith A. Clements, Manuel R. Teixeira, Koveela Govindasami, Michelle Guy, Rosemary A. Wilkinson, Emma J. Sawyer, Angela Morgan, Ed Dicks, Caroline Baynes, Don Conroy, Stig E. Bojesen, Rudolf Kaaks, Daniel Vincent, Francois Bacot, Daniel C. Tessier, Douglas F. Easton, Rosalind A. Eeles

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2520-2528
Number of pages9
JournalHuman Molecular Genetics
Volume22
Issue number12
DOIs
StatePublished - Jun 2013

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Telomerase
Single Nucleotide Polymorphism
Prostatic Neoplasms
Prostate
Logistic Models
Regression Analysis
Gene Expression
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Kote-Jarai, Z., Saunders, E. J., Leongamornlert, D. A., Tymrakiewicz, M., Dadaev, T., Jugurn-Little, S., ... Eeles, R. A. (2013). Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Human Molecular Genetics, 22(12), 2520-2528. https://doi.org/10.1093/hmg/ddt095

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. / Kote-Jarai, Zsofia; Saunders, Edward J.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Jugurn-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, Daniel J; 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.; Easton, Douglas F.; Eeles, Rosalind A.

In: Human Molecular Genetics, Vol. 22, No. 12, 06.2013, p. 2520-2528.

Research output: Contribution to journalArticle

Kote-Jarai, Z, Saunders, EJ, Leongamornlert, DA, Tymrakiewicz, M, Dadaev, T, Jugurn-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, DJ, 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', Human Molecular Genetics, vol. 22, no. 12, pp. 2520-2528. https://doi.org/10.1093/hmg/ddt095
Kote-Jarai Z, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Dadaev T, Jugurn-Little S et al. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Human Molecular Genetics. 2013 Jun;22(12):2520-2528. https://doi.org/10.1093/hmg/ddt095
Kote-Jarai, Zsofia ; Saunders, Edward J. ; Leongamornlert, Daniel A. ; Tymrakiewicz, Malgorzata ; Dadaev, Tokhir ; Jugurn-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, Daniel J ; 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. ; Easton, Douglas F. ; Eeles, Rosalind A. / Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. In: Human Molecular Genetics. 2013 ; Vol. 22, No. 12. pp. 2520-2528.
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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.",
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AU - Kote-Jarai, Zsofia

AU - Saunders, Edward J.

AU - Leongamornlert, Daniel A.

AU - Tymrakiewicz, Malgorzata

AU - Dadaev, Tokhir

AU - Jugurn-Little, Sarah

AU - Ross-Adams, Helen

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Halim, Silvia

AU - Russel, Roslin

AU - Dunning, Alison M.

AU - Luccarini, Craig

AU - Dennis, Joe

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Muir, Ken

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Wiklund, Fredrik

AU - Gronberg, Henrik

AU - Haiman, Christopher A.

AU - Schumacher, Fredrick

AU - Henderson, Brian E.

AU - Marchand, Loic Le

AU - Lindstrom, Sara

AU - Kraft, Peter

AU - Hunter, David J.

AU - Gapstur, Susan

AU - Chanock, Stephen

AU - Berndt, Sonja I.

AU - Albanes, Demetrius

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AU - Schleutker, Johanna

AU - Weischer, Maren

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AU - Riboli, Elio

AU - Key, Tim J.

AU - Travis, Ruth C.

AU - Campa, Daniele

AU - Ingles, Sue A.

AU - John, Esther M.

AU - Hayes, Richard B.

AU - Pharoah, Paul

AU - Khaw, Kay Tee

AU - Stanford, Janet L.

AU - Ostrander, Elaine A.

AU - Signorello, Lisa B.

AU - Thibodeau, Stephen N

AU - Schaid, Daniel J

AU - Maier, Christiane

AU - Vogel, Walther

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Lubinski, Jan

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Park, Jong Y.

AU - Kaneva, Radka

AU - Batra, Jyotsna

AU - Spurdle, Amanda

AU - Clements, Judith A.

AU - Teixeira, Manuel R.

AU - Govindasami, Koveela

AU - Guy, Michelle

AU - Wilkinson, Rosemary A.

AU - Sawyer, Emma J.

AU - Morgan, Angela

AU - Dicks, Ed

AU - Baynes, Caroline

AU - Conroy, Don

AU - Bojesen, Stig E.

AU - Kaaks, Rudolf

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Tessier, Daniel C.

AU - Easton, Douglas F.

AU - Eeles, Rosalind A.

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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.

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