Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer.
Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer.
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DOI：
10.1158/0008-5472.can-08-3151
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发表时间：
2009-03-15
期刊：
影响因子：
11.2
通讯作者：
Chang BL
中科院分区：
文献类型：
--
作者：
Liu W;Sun J;Li G;Zhu Y;Zhang S;Kim ST;Sun J;Wiklund F;Wiley K;Isaacs SD;Stattin P;Xu J;Duggan D;Carpten JD;Isaacs WB;Grönberg H;Zheng SL;Chang BL
我们使用Affymetrix SNP阵列在瑞典一项基于人群的研究（CAPS）中搜索498例侵袭性前列腺癌病例和494例对照者的种系基因组缺失。通过比较整个基因组中约500,000个SNP探针的等位基因强度，观察到在2p24.3处的种系缺失在病例中（12.63%）比对照组（8.28%）更为常见，P=0.028。为了证实这种关联，我们在CAPS和约翰霍普金斯医院（JHH）的其他受试者中对这种种系拷贝数变异（CNV）进行了基因分型。总体而言，在4314例病例和2176例对照中，CNV与前列腺癌风险显著相关（OR = 1.25, 95% CI: 1.06-1.48, P = 0.009）。更重要的是，与非侵袭性前列腺癌（OR = 1.19, 95% CI: 0.98-1.45, P = 0.08）相比，侵袭性前列腺癌（OR = 1.31, 95% CI: 1.08-1.58, P = 0.006）的相关性更强。这种种系CNV的生物学影响是未知的，因为没有已知的基因存在于缺失中。这项研究的结果代表了第一个从全基因组搜索中鉴定出的新型种系CNV，它与前列腺癌风险有显著但中等的相关性。进一步证实这种关联和功能研究是有必要的。
We searched for deletions in the germline genome among 498 aggressive prostate cancer cases and 494 controls from a population-based study in Sweden (CAPS) using Affymetrix SNP arrays. By comparing allele intensities of ∼500,000 SNP probes across the genome, a germline deletion at 2p24.3 was observed to be significantly more common in cases (12.63%) than in controls (8.28%), P=0.028. To confirm the association, we genotyped this germline copy number variation (CNV) in additional subjects from CAPS and from Johns Hopkins Hospital (JHH). Overall, among 4,314 cases and 2,176 controls examined, the CNV was significantly associated with prostate cancer risk (OR = 1.25, 95% CI: 1.06-1.48, P = 0.009). More importantly, the association was stronger for aggressive prostate cancer (OR = 1.31, 95% CI: 1.08-1.58, P = 0.006) than for non-aggressive prostate cancer (OR = 1.19, 95% CI: 0.98-1.45, P = 0.08). The biologic impact of this germline CNV is unknown as no known gene resides in the deletion. Results from this study represent the first novel germline CNV that was identified from a genome-wide search and was significantly, but moderately associated with prostate cancer risk. Additional confirmation of this association and functional studies are warranted.