Multiple novel prostate cancer predisposition loci confirmed by an international study : the PRACTICAL Consortium

Kote-Jarai, Zsofia, Easton, Douglas F., Stanford, Janet L., Ostrander, Elaine A., Schleutker, Johanna, Ingles, Sue A., Schaid, Daniel, Thibodeau, Stephen, Dork, Thilo, Neal, David, Cox, Angela, Maier, Christiane, Vogel, Walter, Guy, Michelle, Muir, Kenneth, Lophatananon, Artitaya, Kedda, Mary-Anne, Spurdle, Amanda B., Steginga, Suzanne K., John, Esther M., Giles, Graham G., Hopper, John, Chappuis, Pierre O., Hutter, Pierre, Foulkes, William D., Hamel, Nancy, Salinas, Claudia A., Koopmeiners, Joseph S., Karyadi, Danielle M., Johanneson, Bo, Wahlfors, Tiina, Tammela, Teuvo L., Stern, Mariana C., Corral, Roman, McDonnell, Shannon K., Schurmann, Peter, Meyer, Andreas, Kuefer, Rainer, Leongamornlert, Daniel A., Tymrakiewicz, Malgorzata, Liu, Jo-fen, O'Mara, Tracy A., Gardiner, R.A. (Frank), Aitken, Joanne F., Joshi, Amit D., Severi, Gianluca, English, Dallas R., Southey, Melissa, Edwards, Stephen M., Al Olama, Ali Amin, The PRACTICAL Consortium, ., Alexander, Kimberly, & Eeles, Rosalind A. (2008) Multiple novel prostate cancer predisposition loci confirmed by an international study : the PRACTICAL Consortium. Cancer Epidemiology Biomarkers and Prevention, 17(8), pp. 2052-2061.

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A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10-17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction.

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ID Code: 17569
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months * Kimberly Alexander was part of the PRACTICAL Consortium
Keywords: Prostate Cancer, Genetics, Epidemiology, Genotyping
DOI: 10.1158/1055-9965.EPI-08-0317
ISSN: 1055-9965
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Genetics not elsewhere classified (060499)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Nursing
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2008 American Association for Cancer Research Inc.
Deposited On: 09 Feb 2009 01:33
Last Modified: 28 Jan 2015 00:16

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