TY - JOUR
T1 - Multiple novel prostate cancer predisposition loci confirmed by an international study
T2 - The PRACTICAL consortium
AU - Kote-Jarai, Zsofia
AU - Easton, Douglas F.
AU - Stanford, Janet L.
AU - Ostrander, Elaine A.
AU - Schleutker, Johanna
AU - Ingles, Sue A.
AU - Schaid, Daniel
AU - Thibodeau, Stephen
AU - Dörk, Thilo
AU - Neal, David
AU - Cox, Angela
AU - Maier, Christiane
AU - Vogel, Walter
AU - Guy, Michelle
AU - Muir, Kenneth
AU - Lophatananon, Artitaya
AU - Kedda, Mary Anne
AU - Spurdle, Amanda
AU - Steginga, Suzanne
AU - John, Esther M.
AU - Giles, Graham
AU - Hopper, John
AU - Chappuis, Pierre O.
AU - Hutter, Pierre
AU - Foulkes, William D.
AU - Hamel, Nancy
AU - Salinas, Claudia A.
AU - Koopmeiners, Joseph S.
AU - Karyadi, Danielle M.
AU - Johanneson, Bo
AU - Wahlfors, Tiina
AU - Tammela, Teuvo L.
AU - Stern, Mariana C.
AU - Corral, Roman
AU - McDonnell, Shannon K.
AU - Schürmann, Peter
AU - Meyer, Andreas
AU - Kuefer, Rainer
AU - Leongamornlert, Daniel A.
AU - Tymrakiewicz, Malgorzata
AU - Liu, Jo Fen
AU - O'Mara, Tracy
AU - Gardiner, R. A.
AU - Aitken, Joanne
AU - Joshi, Amit D.
AU - Severi, Gianluca
AU - English, Dallas R.
AU - Southey, Melissa
AU - Edwards, Stephen M.
AU - Al Olama, Ali Amin
AU - Eeles, Rosalind A.
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-08-0317
DO - 10.1158/1055-9965.EPI-08-0317
M3 - Article
C2 - 18708398
AN - SCOPUS:54049139306
SN - 1055-9965
VL - 17
SP - 2052
EP - 2061
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 8
ER -