Genome-wide analysis of the role of copy-number variation in pancreatic cancer risk.
Genome-wide analysis of the role of copy-number variation in pancreatic cancer risk.
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DOI：
10.3389/fgene.2014.00029
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发表时间：
2014
影响因子：
3.7
通讯作者：
Klein RJ
中科院分区：
文献类型：
--
作者：
Willis JA;Mukherjee S;Orlow I;Viale A;Offit K;Kurtz RC;Olson SH;Klein RJ
尽管家族史是胰腺腺癌的一个风险因素，但这种疾病的大部分遗传病因仍然未知。虽然全基因组关联研究已经确定了一些与胰腺癌风险相关的常见单核苷酸多态性（SNP），但这些SNP并不能解释这种疾病的所有遗传度。我们假设基因组中的拷贝数变异（CNV）可能在胰腺腺癌的遗传易感性中起作用。在此，我们报告了一项在一个基于医院的小型欧洲血统胰腺癌病例和对照队列中进行的全基因组CNV分析。使用Illumina Human CNV370平台在223例胰腺癌病例（包括散发性和家族性）和169例对照中进行了生殖系CNV的发现。经过严格的质量控制，我们探究了总体CNV负荷是否是胰腺癌的一个风险因素。最后，我们进行了计算机模拟CNV基因分型和关联测试以发现新的CNV风险位点。当我们检查总体CNV负荷时，我们没有发现强有力的证据表明CNV负荷在胰腺癌风险中起作用，无论是在总体上还是在有该疾病家族史的个体中。同样，我们没有看到任何显著的证据表明任何特定的CNV与胰腺癌风险相关。综上所述，这些数据表明CNV对胰腺癌的遗传病因没有实质性贡献，尽管结果受到样本量小以及基于阵列的CNV研究中固有的较大实验变异性的影响。
Although family history is a risk factor for pancreatic adenocarcinoma, much of the genetic etiology of this disease remains unknown. While genome-wide association studies have identified some common single nucleotide polymorphisms (SNPs) associated with pancreatic cancer risk, these SNPs do not explain all the heritability of this disease. We hypothesized that copy number variation (CNVs) in the genome may play a role in genetic predisposition to pancreatic adenocarcinoma. Here, we report a genome-wide analysis of CNVs in a small hospital-based, European ancestry cohort of pancreatic cancer cases and controls. Germline CNV discovery was performed using the Illumina Human CNV370 platform in 223 pancreatic cancer cases (both sporadic and familial) and 169 controls. Following stringent quality control, we asked if global CNV burden was a risk factor for pancreatic cancer. Finally, we performed in silico CNV genotyping and association testing to discover novel CNV risk loci. When we examined the global CNV burden, we found no strong evidence that CNV burden plays a role in pancreatic cancer risk either overall or specifically in individuals with a family history of the disease. Similarly, we saw no significant evidence that any particular CNV is associated with pancreatic cancer risk. Taken together, these data suggest that CNVs do not contribute substantially to the genetic etiology of pancreatic cancer, though the results are tempered by small sample size and large experimental variability inherent in array-based CNV studies.
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影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-10-3431
发表时间：
2011-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Vincent A;Omura N;Hong SM;Jaffe A;Eshleman J;Goggins M
通讯作者：
Goggins M
影响因子：
14.9
作者：
Diskin SJ;Li M;Hou C;Yang S;Glessner J;Hakonarson H;Bucan M;Maris JM;Wang K
通讯作者：
Wang K
影响因子：
30.8
作者：
Barnes, Chris;Plagnol, Vincent;Fitzgerald, Tomas;Redon, Richard;Marchini, Jonathan;Clayton, David;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.