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 Jugurnauth-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 Severi; Fredrik 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; Stig E Bojesen; COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative

doi:10.1093/hmg/ddt086

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 Jugurnauth-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, Stig E Bojesen, COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative

94 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Human Molecular Genetics
Vol/bind	22
Udgave nummer	12
Sider (fra-til)	2520-8
Antal sider	9
ISSN	0964-6906
DOI	https://doi.org/10.1093/hmg/ddt086
Status	Udgivet - 15 jun. 2013

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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., ... COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative (2013). Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Human Molecular Genetics, 22(12), 2520-8. https://doi.org/10.1093/hmg/ddt086

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, Le Marchand, L, 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, K-T, Stanford, JL, Ostrander, EA, Signorello, LB, Bojesen, SE & COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative 2013, 'Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression', Human Molecular Genetics, bind 22, nr. 12, s. 2520-8. https://doi.org/10.1093/hmg/ddt086

@article{1035d971528f4b7cb999e498769d2b35,

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 = "Zsofia Kote-Jarai and Saunders, {Edward J} and Leongamornlert, {Daniel A} and Malgorzata Tymrakiewicz and Tokhir Dadaev and Sarah Jugurnauth-Little and Helen Ross-Adams and {Al Olama}, {Ali Amin} and Sara Benlloch and Silvia Halim and Roslin Russel and Dunning, {Alison M} and Craig Luccarini and Joe Dennis and Neal, {David E} and Hamdy, {Freddie C} and Donovan, {Jenny L} and Ken Muir and Giles, {Graham G} and Gianluca Severi and Fredrik Wiklund and Henrik Gronberg and Haiman, {Christopher A} and Fredrick Schumacher and Henderson, {Brian E} and {Le Marchand}, Loic and Sara Lindstrom and Peter Kraft and Hunter, {David J} and Susan Gapstur and Stephen Chanock and Berndt, {Sonja I} and Demetrius Albanes and Gerald Andriole and Johanna Schleutker and Maren Weischer and Federico Canzian and Elio Riboli and Key, {Tim J} and Travis, {Ruth C} and Daniele Campa and Ingles, {Sue A} and John, {Esther M} and Hayes, {Richard B} and Paul Pharoah and Kay-Tee Khaw and Stanford, {Janet L} and Ostrander, {Elaine A} and Signorello, {Lisa B} and Bojesen, {Stig E} and {COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative}",

year = "2013",

month = jun,

day = "15",

doi = "10.1093/hmg/ddt086",

language = "English",

volume = "22",

pages = "2520--8",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "12",

}

TY - JOUR

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

AU - Kote-Jarai, Zsofia

AU - Saunders, Edward J

AU - Leongamornlert, Daniel A

AU - Tymrakiewicz, Malgorzata

AU - Dadaev, Tokhir

AU - Jugurnauth-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 - Le Marchand, Loic

AU - Lindstrom, Sara

AU - Kraft, Peter

AU - Hunter, David J

AU - Gapstur, Susan

AU - Chanock, Stephen

AU - Berndt, Sonja I

AU - Albanes, Demetrius

AU - Andriole, Gerald

AU - Schleutker, Johanna

AU - Weischer, Maren

AU - Canzian, Federico

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 - Bojesen, Stig E

AU - COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative

PY - 2013/6/15

Y1 - 2013/6/15

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 - Journal article

C2 - 23535824

SN - 0964-6906

VL - 22

SP - 2520

EP - 2528

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 12

ER -

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

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