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, Steginga, Suzanne, John, Esther M., Giles, Graham, 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, Gardiner, R. A. (Frank), Aitken, Joanne, Joshi, Amit D., Severi, Gianluca, English, Dallas R., Southey, Melissa, Edwards, Stephen M., Al Olama, Ali Amin, The PRACTICAL Consortium and 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: 2052-2061. doi:10.1158/1055-9965.EPI-08-0317


Author 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
Steginga, Suzanne
John, Esther M.
Giles, Graham
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
Gardiner, R. A. (Frank)
Aitken, Joanne
Joshi, Amit D.
Severi, Gianluca
English, Dallas R.
Southey, Melissa
Edwards, Stephen M.
Al Olama, Ali Amin
The PRACTICAL Consortium
Eeles, Rosalind A.
Title Multiple novel prostate cancer predisposition loci confirmed by an international study: The PRACTICAL consortium
Journal name Cancer Epidemiology Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
Publication date 2008-08-01
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-08-0317
Open Access Status DOI
Volume 17
Issue 8
Start page 2052
End page 2061
Total pages 10
Editor John D Potter
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Subject C1
920504 Men's Health
111799 Public Health and Health Services not elsewhere classified
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 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 (950% 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.
Keyword Genome-wide Association
Susceptibility
Risk
Inheritance
Androgen
Binding
Variant
Gene
Q-Index Code C1
Q-Index Status Confirmed Code

 
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