Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.
Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.
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DOI：
10.1371/journal.pone.0035307
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ostrowski J
中科院分区：
文献类型：
--
作者：
Gaj P;Maryan N;Hennig EE;Ledwon JK;Paziewska A;Majewska A;Karczmarski J;Nesteruk M;Wolski J;Antoniewicz AA;Przytulski K;Rutkowski A;Teumer A;Homuth G;Starzyńska T;Regula J;Ostrowski J
前列腺癌（PCa）和结肠直肠癌（CRC）是波兰最常见的诊断癌症和与癌症相关的死亡原因。迄今为止，已经确定了许多与两种癌症易感性相关的单核苷酸多态性（snp），但它们对疾病风险的影响可能因人群而异。为了确定波兰人群中与PCa和CRC相关的新SNP，使用Affymetrix genome-wide Human SNP 6.0阵列的DNA样本池进行了一项全基因组关联研究（GWAS）。共纳入135例前列腺癌患者和270名健康男性（前列腺癌亚研究），525例腺瘤（AD）患者，630例结直肠癌患者和690名对照组（AD/CRC亚研究）。等位基因频率分布比较采用t检验和χ2检验。只选择那些与代理SNP显著相关的SNP （p<0.001；距离为100 kb； r2>0.7）。采用PLINK进行GWAS标记选择。该研究通过扩大患者和对照组的队列进行了重复研究。还研究了与先前报道的PCa和CRC易感性变异的关系。个体患者采用TaqMan SNP基因分型法进行基因分型。GWAS分别选择了6个和24个新的与PCa和CRC易感性相关的候选snp。在重复研究中，这些关联中有17个在加性遗传模型中被证实为显著的。其中7项经多重假设检验校正后仍显著。此外，已经确定了17个先前报告的风险变异，其中5个在纠正后仍然显着。Pooled-DNA GWAS能够在波兰人群中鉴定出新的结直肠癌易感位点。先前报道的CRC和PCa易感性变异也被确定，验证了它们之间的关联的全局性。需要进一步的独立复制研究来证实新发现的候选易感位点的重要性。
Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations. To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ2-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r2>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays. The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction. Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.
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影响因子：
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作者：
Beebe-Dimmer, Jennifer L.;Levin, Albert M.;Douglas, Julie A.
通讯作者：
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通讯作者：
Skol, Andrew
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
64.8
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