Data from Refining the Prostate Cancer Genetic Association within the <i>JAZF1</i> Gene on Chromosome 7p15.2

<div>Abstract<p><b>Background</b>: 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 <i>JAZF1</i> gene on chromosome 7p15.2, showed a promising association with PrCa overall (<i>P</i> = 2.14 × 10<sup>−6</sup>), with a suggestion of stronger association with aggressive disease (<i>P</i> = 1.2 × 10<sup>−7</sup>).</p><p><b>Methods</b>: In the third stage of genome-wide association studies, we genotyped 106 <i>JAZF1</i> SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry.</p><p><b>Results</b>: The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [<i>P</i> = 7.79 × 10<sup>−11</sup>; OR<sub>HET</sub>, 1.19 (95% confidence interval, 1.12-1.27); OR<sub>HOM</sub>, 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 (<i>P</i> = 1.60 × 10<sup>−4</sup> for aggressive cancer, <i>n</i> = 4,597; <i>P</i> = 3.25 × 10<sup>−8</sup> for nonaggressive cancer, <i>n</i> = 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 <i>JAZF1</i> previously associated with height (rs849140; <i>P</i> = 0.587), body stature (rs849141, tagged by rs849136; <i>P</i> = 0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; <i>P</i> = 0.657).</p><p><b>Conclusion</b>: rs10486567 remains the most significant marker for PrCa risk within <i>JAZF1</i> in individuals of European ancestry.</p><p><b>Impact</b>: Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa. Cancer Epidemiol Biomarkers Prev; 19(5); 1349–55. ©2010 AACR.</p></div>