Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

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

The UK Genetic Prostate Cancer Study Collaborative/British Association of Urological Surgeons' Section of Oncology

The UK ProtecT Study Collaborators

The PRACTICAL Consortium
Data(s)

01/03/2013
Resumo

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.
Formato

application/pdf
Identificador

http://eprints.qut.edu.au/57055/
Publicador

Oxford University Press
Relação

http://eprints.qut.edu.au/57055/1/__staffhome.qut.edu.au_staffgrouph%24_hollambc_Desktop_2520.full.pdf

DOI:10.1093/hmg/ddt086

Kote-Jarai, Z., Saunders, E., Leongamornlert, D.A., Tymrakiewicz, M., Dadaev, T., Jugurnath-Little, S., Ross-Adams, H., Amin Ali, A.L., Benlloch, S., Halim, S., Russel, R., Ghoussaini, M., Luccarini, C., Dennis, J., Neal, D.E., Hamdy, F.C., Donovan, J.L., Muir, K.R., Giles, G.G., Severi, G., Wiklund, F., Gronberg, H., Haiman, C.A., Schumacher, F.R., Henderson, B.E., Le Marchand, L., Lindstrom, S., Kraft, P., Hunter, D.J., Gapstur, S., Chanock, S., Berndt, S.I., Albanes, D., Andriole, G., Schleutker, J., Weischer, M., Canzian, F., Riboli, E., Key, T.J., Travis, R.C., Campa, D., Ingles, S., John, E.M., Hayes, R.B., Pharoah, P., Pashayan, N., Khaw, K-T, Stanford, J.L., Ostrander, E.A., Signorello, L.B., Thobodeau, S.N, Schaid, D., Maier, C., Vogel, W., Kibel, A.S, Cybulski, C., Lubinski, J., Cannon-Albright, L., Brenner, H., Park, J.Y., Kaneva, R., Batra, J., Spurdle, A., Clements, J., Teixeira, M.R., Dicks, E., Lee, A., Dunning, A.M., Baynes, C., Conroy, D.K., Govindasami, K., Guy, M., Wilkinson, R.A., Sawyer, E.J., Morgan, A., Vincent, D., Bacot, F., Tessier, D.C., Easton, D.F., & Eeles, R.A. (2013) Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression. Human Molecular Genetics, 22(12), pp. 2520-2528.
Direitos

Copyright 2013 The Authors

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/ 3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permission@oup.com
Fonte

School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #060407 Genome Structure and Regulation
Tipo

Journal Article
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