Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression
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.
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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|Item Type:||Journal Article|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Genome Structure and Regulation (060407)|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2013 The Authors|
|Copyright Statement:||This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/
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|Deposited On:||11 Feb 2013 01:13|
|Last Modified:||30 Jan 2015 05:03|
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