Nam R K, Zhang W W, Loblaw D A, Klotz L H, Trachtenberg J, Jewett M A S, Stanimirovic A, Davies T O, Toi A, Venkateswaran V, Sugar L, Siminovitch K A, Narod S A
Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Prostate Cancer Prostatic Dis. 2008;11(3):241-6. doi: 10.1038/sj.pcan.4501010. Epub 2007 Sep 18.
We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.
我们使用Affymetrix 10000 SNP基因芯片对3090例散发性前列腺癌患者及对照进行了全基因组关联研究。对40例前列腺癌病例和40例非癌对照的初步筛查发现237个单核苷酸多态性（SNP）与前列腺癌相关（P<0.05）。在这些SNP中，选择了33个对2069例接受过癌症筛查前列腺活检的男性进行进一步的关联分析。结果在这个更大的样本中确定了5个位点与前列腺癌风险增加显著相关（rs 1930293，比值比[OR]=1.7，P=0.03；rs 717809 - 2p12，OR=1.3，P=0.03；rs 494770 - 4q34，OR=1.3，P=0.01；rs 2348763 - 7p21，OR=1.5，P=0.01；rs 1552895 - 9p22，OR=1.5，P=0.002）。为验证这些关联数据，在该研究队列以及另外1021名男性（总研究对象数=3090）中对跨越后5个位点的61个额外的HapMap标签SNP进行基因分型。该分析显示标签SNP rs 4568789（1号染色体q25区域）和标签SNP rs 13225697（7号染色体p21区域）与前列腺癌显著相关（P值分别为0.009和0.0
