候选基因甲基化与腺瘤性息肉形成的病例对照研究。
Case-control study of candidate gene methylation and adenomatous polyp formation.
作者信息
Alexander M, Burch J B, Steck S E, Chen C-F, Hurley T G, Cavicchia P, Shivappa N, Guess J, Zhang H, Youngstedt S D, Creek K E, Lloyd S, Jones K, Hébert J R
机构信息
South Carolina Statewide Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, USA.
Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene St, Room 228, Columbia, SC, 29209, USA.
出版信息
Int J Colorectal Dis. 2017 Feb;32(2):183-192. doi: 10.1007/s00384-016-2688-1. Epub 2016 Oct 22.
PURPOSE
Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation.
METHODS
Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios (ORs) and 95 % confidence intervals (95% CIs) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders.
RESULTS
Complete data were available for 107 participants; 36 % had adenomas (men 40 %, women 31 %). Hypomethylation of the MINT1 locus (OR 5.3, 95% CI 1.0-28.2) and the PER1 (OR 2.9, 95% CI 1.1-7.7) and PER3 (OR 11.6, 95% CI 1.6-78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71-97 %), sensitivity was relatively low (18-45 %).
CONCLUSION
Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance.
目的
结直肠癌（CRC）是最常见且可预防的癌症形式之一，但仍是癌症相关死亡的第二大主要原因。结直肠腺瘤是70 - 90%的CRC病例中出现的前驱病变。识别腺瘤的外周生物标志物将有助于加强筛查工作。这项探索性研究检测了外周血白细胞中20个候选标志物的甲基化状态及其与腺瘤形成的关联。
方法
从当地一家内镜诊所招募的患者提供了知情同意书，并完成了一项访谈，以确定人口统计学、生活方式和腺瘤风险因素。病例为经组织病理学确诊的腺瘤患者，对照包括结肠镜检查正常的患者或组织病理学检查结果无需加强监测的患者（正常活检、增生性息肉）。甲基化特异性聚合酶链反应用于表征候选基因启动子甲基化。使用无条件多变量逻辑回归计算比值比（OR）和95%置信区间（95%CI），以检验在调整混杂因素后候选基因甲基化在病例和对照之间存在差异的假设。
结果
107名参与者有完整数据；36%患有腺瘤（男性40%，女性31%）。MINT1基因座（OR 5.3，95%CI 1.0 - 28.2）以及PER1（OR 2.9，95%CI 1.1 - 7.7）和PER3（OR 11.6，95%CI 1.6 - 78.5）时钟基因启动子的低甲基化在腺瘤病例中更常见。虽然这三种标志物的特异性为中度至高度（71 - 97%），但敏感性相对较低（18 - 45%）。
结论
建议对这些表观遗传标志物进行随访，以进一步评估它们在腺瘤筛查或监测中的效用。
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