Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.
Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.
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DOI：
10.1158/1055-9965.epi-09-1181
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发表时间：
2010-05
期刊：
影响因子：
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通讯作者：
Yeager M
中科院分区：
文献类型：
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作者：
Prokunina-Olsson L;Fu YP;Tang W;Jacobs KB;Hayes RB;Kraft P;Berndt SI;Wacholder S;Yu K;Hutchinson A;Spencer Feigelson H;Thun MJ;Diver WR;Albanes D;Virtamo J;Weinstein S;Schumacher FR;Cancel-Tassin G;Cussenot O;Valeri A;Andriole GL;Crawford ED;Haiman CA;Henderson BE;Kolonel L;Le Marchand L;Siddiq A;Riboli E;Travis R;Kaaks R;Isaacs WB;Isaacs SD;Grönberg H;Wiklund F;Xu J;Vatten LJ;Hveem K;Kumle M;Tucker M;Hoover RN;Fraumeni JF Jr;Hunter DJ;Thomas G;Chatterjee N;Chanock SJ;Yeager M
全基因组关联研究（GWAS）已经确定了与前列腺癌（PrCa）易感性相关的多种遗传变异。在两阶段癌症易感性遗传标志物（CGEMS）前列腺癌扫描中，位于染色体7p15.2上JAZF 1基因内含子2内的单核苷酸多态性（SNP）rs 10486567显示出与PrCa整体（p = 2.14×10−6）有希望的关联，并建议与侵袭性疾病（p = 1.2×10−7）有更强的关联。在GWAS的第三阶段，我们对10，286例PrCa病例和9，135例欧洲血统对照的106个JAZF 1 SNP进行了基因分型。与初始标记rs 10486567观察到最强的关联，其现在达到全基因组显著性（p = 7.79×10−11，ORHET 1.19; 95%CI = 1.12 - 1.27和ORHOM 1.37; 95%CI = 1.20 - 1.56）。我们没有证实先前的建议，即rs 10486567与侵袭性疾病有更强的关联（侵袭性癌症p = 1.60×10−4，n= 4，597;非侵袭性癌症p = 3.25×10−8，n= 4，514）。基于多基因座模型与调整rs 10486567，没有额外的独立信号观察到染色体7p15.2。PrCa风险与JAZF 1中先前与身高（rs 849140，p = 0.587），身材（rs 849141，由rs 849136标记，p = 0.171），2型糖尿病和系统性红斑狼疮风险（rs 864745，由rs 849142标记，p = 0.657）相关的SNP之间没有关联。rs 10486567仍然是欧洲血统个体中JAZF 1内PrCa风险的最重要标志物。未来的研究应确定rs 10486567高LD的所有变体，并评估其对PrCa的功能意义。
Genome-wide association studies (GWAS) have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility (CGEMS) 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 = 1.2×10−7). In the third stage of GWAS, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. The strongest association was observed with the initial marker, rs10486567, which now achieves genome-wide significance (p = 7.79×10−11, ORHET 1.19; 95%CI = 1.12 – 1.27 and ORHOM 1.37; 95%CI = 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 = 3.25×10−8 for non-aggressive cancer, n=4,514). Based on a multi-locus 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), risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142, p = 0.657). rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. Future studies should identify all variants in high LD with rs10486567 and evaluate their functional significance for PrCa.