Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON Canada M5G 2 M9 ; Dalla Lana School of Public Health, University of Toronto, Toronto, ON Canada M5T 3M7.
Dalla Lana School of Public Health, University of Toronto, Toronto, ON Canada M5T 3M7.
Biomark Res. 2015 Mar 19;3:6. doi: 10.1186/s40364-015-0031-6. eCollection 2015.
In this study we performed genome-wide association studies to identify candidate SNPs that may predict the risk of disease outcome in colorectal cancer.
Patient cohort consisted of 505 unrelated patients with Caucasian ancestry. Germline DNA samples were genotyped using the Illumina® human Omni-1quad SNP chip. Associations of SNPs with overall and disease free survivals were examined primarily for 431 patients with microsatellite instability-low (MSI-L) or stable (MSS) colorectal tumors using Cox proportional hazards method adjusting for clinical covariates. Bootstrap method was applied for internal validation of results. As exploratory analyses, association analyses for the colon (n = 334) and rectal (n = 171) cancer patients were also performed.
As a result, there was no SNP that reached the genomewide significance levels (p < 5x10(-8)) in any of the analyses. A small number of genetic markers (n = 10) showed nominal associations (p <10(-6)) for MSS/MSI-L, colon, or rectal cancer patient groups. These markers were located in two non-coding RNA genes or intergenic regions and none were amino acid substituting polymorphisms. Bootstrap analysis for the MSS/MSI-L cohort data suggested the robustness of the observed nominal associations.
Likely due to small number of patients, our study did not identify an acceptable level of association of SNPs with outcome in MSS/MSI-L, colon, or rectal cancer patients. A number of SNPs with sub-optimal p-values were, however, identified; these loci may be promising and examined in other larger-sized patient cohorts.
本研究进行了全基因组关联研究，以鉴定可能预测结直肠癌疾病结局风险的候选 SNP。
患者队列包括 505 名无亲缘关系的白种人患者。使用 Illumina®人类 Omni-1quad SNP 芯片对患者的种系 DNA 样本进行基因分型。使用 Cox 比例风险方法，对 431 名微卫星不稳定性低（MSI-L）或稳定（MSS）结直肠肿瘤患者的 SNP 与总生存和无病生存的相关性进行了主要分析，同时调整了临床协变量。采用自举法对内部分析结果进行验证。作为探索性分析，还对结肠癌（n=334）和直肠癌（n=171）患者进行了相关性分析。
结果显示，在任何分析中，都没有 SNP 达到全基因组显著性水平（p<5x10(-8))。少数遗传标记（n=10）在 MSS/MSI-L、结肠癌或直肠癌患者组中显示出名义关联（p<10(-6))。这些标记位于两个非编码 RNA 基因或基因间区域，没有一个是氨基酸替换多态性。对 MSS/MSI-L 队列数据的自举分析表明，观察到的名义相关性具有稳健性。
可能由于患者数量较少，我们的研究没有发现 SNP 与 MSS/MSI-L、结肠癌或直肠癌患者结局之间具有可接受水平的关联。然而，确定了一些具有次优 p 值的 SNP；这些位点可能具有前景，可在其他更大规模的患者队列中进行研究。
