TY - JOUR
T1 - Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2
AU - Prokunina-Olsson, Ludmila
AU - Fu, Yi Ping
AU - Tang, Wei
AU - Jacobs, Kevin B.
AU - Hayes, Richard B.
AU - Kraft, Peter
AU - Berndt, Sonja I.
AU - Wacholder, Sholom
AU - Yu, Kai
AU - Hutchinson, Amy
AU - Feigelson, Heather Spencer
AU - Thun, Michael J.
AU - Diver, W. Ryan
AU - Albanes, Demetrius
AU - Virtamo, Jarmo
AU - Weinstein, Stephanie
AU - Schumacher, Fredrick R.
AU - Cancel-Tassin, Geraldine
AU - Cussenot, Olivier
AU - Valeri, Antoine
AU - Andriole, Gerald L.
AU - Crawford, E. David
AU - Haiman, Christopher A.
AU - Henderson, Brian E.
AU - Kolonel, Laurence
AU - Le Marchand, Loic
AU - Siddiq, Afshan
AU - Riboli, Elio
AU - Travis, Ruth
AU - Kaaks, Rudolf
AU - Isaacs, William B.
AU - Isaacs, Sarah D.
AU - Grönberg, Henrik
AU - Wiklund, Fredrik
AU - Xu, Jianfeng
AU - Vatten, Lars J.
AU - Hveem, Kristian
AU - Kumle, Merethe
AU - Tucker, Margaret
AU - Hoover, Robert N.
AU - Fraumeni, Joseph F.
AU - Hunter, David J.
AU - Thomas, Gilles
AU - Chatterjee, Nilanjan
AU - Chanock, Stephen J.
AU - Yeager, Meredith
PY - 2010/5
Y1 - 2010/5
N2 - Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10-6), with a suggestion of stronger association with aggressive disease (P = 1.2 x 10-7). Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10-11; OR HET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10-4 for aggressive cancer, n = 4,597; P = 3.25 x 10-8 for non-aggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657). Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa.
AB - Background: Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P = 2.14 × 10-6), with a suggestion of stronger association with aggressive disease (P = 1.2 x 10-7). Methods: In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. Results: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P = 7.79 × 10-11; OR HET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P = 1.60 × 10-4 for aggressive cancer, n = 4,597; P = 3.25 x 10-8 for non-aggressive cancer, n = 4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P = 0.587), body stature (rs849141, tagged by rs849136; P = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P = 0.657). Conclusion: rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. Impact: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa.
UR - http://www.scopus.com/inward/record.url?scp=77952047322&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-09-1181
DO - 10.1158/1055-9965.EPI-09-1181
M3 - Article
C2 - 20406958
AN - SCOPUS:77952047322
SN - 1055-9965
VL - 19
SP - 1349
EP - 1355
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -