Multiple novel prostate cancer predisposition loci confirmed by an international study: The PRACTICAL consortium

Zsofia Kote-Jarai, Douglas F. Easton, Janet L. Stanford, Elaine A. Ostrander, Johanna Schleutker, Sue A. Ingles, Daniel Schaid, Stephen Thibodeau, Thilo Dörk, David Neal, Angela Cox, Christiane Maier, Walter Vogel, Michelle Guy, Kenneth Muir, Artitaya Lophatananon, Mary Anne Kedda, Amanda Spurdle, Suzanne Steginga, Esther M. JohnGraham Giles, John Hopper, Pierre O. Chappuis, Pierre Hutter, William D. Foulkes, Nancy Hamel, Claudia A. Salinas, Joseph S. Koopmeiners, Danielle M. Karyadi, Bo Johanneson, Tiina Wahlfors, Teuvo L. Tammela, Mariana C. Stern, Roman Corral, Shannon K. McDonnell, Peter Schürmann, Andreas Meyer, Rainer Kuefer, Daniel A. Leongamornlert, Malgorzata Tymrakiewicz, Jo Fen Liu, Tracy O'Mara, R. A. Gardiner, Joanne Aitken, Amit D. Joshi, Gianluca Severi, Dallas R. English, Melissa Southey, Stephen M. Edwards, Ali Amin Al Olama, Rosalind A. Eeles

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

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 eachg enotype 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 perallele 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.

Original languageEnglish (US)
Pages (from-to)2052-2061
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number8
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Kote-Jarai, Z., Easton, D. F., Stanford, J. L., Ostrander, E. A., Schleutker, J., Ingles, S. A., Schaid, D., Thibodeau, S., Dörk, T., Neal, D., Cox, A., Maier, C., Vogel, W., Guy, M., Muir, K., Lophatananon, A., Kedda, M. A., Spurdle, A., Steginga, S., ... Eeles, R. A. (2008). Multiple novel prostate cancer predisposition loci confirmed by an international study: The PRACTICAL consortium. Cancer Epidemiology Biomarkers and Prevention, 17(8), 2052-2061. https://doi.org/10.1158/1055-9965.EPI-08-0317