Genome-wide copy-number variation analysis identifies common genetic variants at 20p13 associated with aggressiveness of prostate cancer
Genome-wide copy-number variation analysis identifies common genetic variants at 20p13 associated with aggressiveness of prostate cancer
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DOI：
10.1093/carcin/bgr082
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发表时间：
2011-07-01
期刊：
影响因子：
4.7
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
--
作者：
Jin, Guangfu;Sun, Jishan;Xu, Jianfeng
前列腺癌（PCa）侵袭性的遗传决定因素尚不清楚。拷贝数变异（CNVs）是遗传多样性的主要来源之一，对细胞生物学和人类疾病具有重要的调节作用。我们假设CNVs可能与前列腺癌侵袭性有关。为了验证这一假设，我们使用Affymetrix 6.0阵列对来自约翰霍普金斯医院（JHH1）的448例侵袭性和500例非侵袭性PCa患者进行了全基因组共同CNVs分析。在另外2895例侵袭性和3094例非侵袭性病例中，包括来自JHH研究（jh2）、NCI癌症易感性遗传标记（CGEMS）研究和瑞典前列腺癌（CAPS）研究的剩余病例受试者，使用标记感兴趣CNVs的单核苷酸多态性（snp）进一步证实了暗含的关联。我们发现，在20p13位点有32.3 kb缺失多态性的CNP2454与jh1中PCa的侵袭性显著相关[比值比(OR) = 1.30, 95%可信区间（CI）： 1.01-1.68；P = 0.045]。CNP2454的最佳标记SNP rs2209313被用于在jh1 （P = 0.045）和所有确认研究人群中证实这一发现（P = 1.77 × 10(-3)）。所有3353例侵袭性和3584例非侵袭性病例的汇总分析显示，rs2209313的T等位基因与侵袭性PCa风险增加显著相关（OR = 1.17, 95% CI: 1.07-1.27; P = 2.75 × 10(-4)）。我们的研究结果表明，20p13的遗传变异可能是导致前列腺癌进展的原因。
The genetic determinants for aggressiveness of prostate cancer (PCa) are poorly understood. Copy-number variations (CNVs) are one of the major sources for genetic diversity and critically modulate cellular biology and human diseases. We hypothesized that CNVs may be associated with PCa aggressiveness. To test this hypothesis, we conducted a genome-wide common CNVs analysis in 448 aggressive and 500 nonaggressive PCa cases recruited from Johns Hopkins Hospital (JHH1) using Affymetrix 6.0 arrays. Suggestive associations were further confirmed using single-nucleotide polymorphisms (SNPs) that tagged the CNVs of interest in an additional 2895 aggressive and 3094 nonaggressive cases, including those from the remaining case subjects of the JHH study (JHH2), the NCI Cancer Genetic Markers of Susceptibility (CGEMS) Study, and the CAncer of the Prostate in Sweden (CAPS) Study. We found that CNP2454, a 32.3 kb deletion polymorphism at 20p13, was significantly associated with aggressiveness of PCa in JHH1 [ odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.68; P = 0.045]. The best-tagging SNP for CNP2454, rs2209313, was used to confirm this finding in both JHH1 (P = 0.045) and all confirmation study populations combined (P = 1.77 x 10(-3)). Pooled analysis using all 3353 aggressive and 3584 nonaggressive cases showed the T allele of rs2209313 was significantly associated with an increased risk of aggressive PCa (OR = 1.17, 95% CI: 1.07-1.27; P = 2.75 x 10(-4)). Our results indicate that genetic variations at 20p13 may be responsible for the progression of PCa.