Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN 37203, USA.
Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1219-26. doi: 10.1158/1055-9965.EPI-12-1437. Epub 2013 May 15.
Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown.
In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis.
No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)).
This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies.
These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.
结直肠癌是癌症相关死亡的第二大主要原因，大多数结直肠癌通常源自结直肠腺瘤。切除息肉可降低结直肠癌的死亡率。已知结直肠腺瘤在家族中聚集；然而，导致息肉风险的遗传决定因素在很大程度上尚不清楚。
在这项研究中，我们使用了田纳西州结肠息肉研究和田纳西州-印第安纳州腺瘤复发研究的数据，对腺瘤病例和对照进行了全基因组关联研究。我们的设计包括发现和复制阶段，共有 2551 名白种人腺瘤病例和 3285 名白种人对照。我们进行了逻辑回归分析，以检验发现和复制阶段的关联，并进一步通过荟萃分析检查了结果。
没有单个核苷酸多态性（SNP）达到全基因组显著 P 值；然而，最显著相关的 SNP 要么是先前在全基因组关联研究中与结直肠癌相关的 SNP，如基因 POU5F1 中的 rs10505477[比值比（OR）=0.87；95%置信区间（CI）0.81-0.94；P=4.4×10(-4)]，要么与其他组织中的良性生长具有生物学联系，如基因组蛋白去乙酰化酶 9 中的 rs1919314[OR=1.32；95%置信区间（CI）1.18-1.47；P=1.1×10(-6)]。
本研究表明，一些 SNP 可能与腺瘤风险相关，并为未来的研究提供了线索。
这些结果表明，一些已知的结直肠癌遗传风险因素是必要的，但不足以致癌。
