Genomic Aberrations Occurring in Subsets of Serrated Colorectal Lesions but not Conventional Adenomas
Genomic Aberrations Occurring in Subsets of Serrated Colorectal Lesions but not Conventional Adenomas
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DOI：
10.1158/0008-5472.can-12-3462
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发表时间：
2013-05-01
期刊：
影响因子：
11.2
通讯作者：
Makar, Karen W.
中科院分区：
文献类型：
--
作者：
Burnett-Hartman, Andrea N.;Newcomb, Polly A.;Makar, Karen W.
侵袭性结直肠癌的一个子集表现出BRAF突变，MLH 1甲基化和CpG岛甲基化表型（CIMP），但前体并不明确。在这项研究中，我们确定了这些标志物在结直肠息肉中的状态，并评估了相关的危险因素。该研究包括771例息肉病例和1，027例对照，年龄在24至80岁之间，是一个团体健康计划的一部分，从1998年到2007年接受了结肠镜检查，并完成了评估风险因素的结构化问卷。在标准病理学检查后，分析息肉的BRAF突变（V600 E）并测试MLH 1和CIMP甲基化，后者包括基因CACNA 1G、IGF 2、NEUROG 1、RUNX 3和SOCS 1。多分类逻辑回归用于估计息肉分子定义亚群与潜在危险因素之间关联的OR和95%置信区间。成功检测了580个常规腺瘤和419个锯齿状病变。对于腺瘤，结肠右侧/盲肠区域中每种标记物的患病率≤ 10 mm。CIMP高锯齿状病变的危险因素包括白人种族、当前吸烟状况和息肉病史，而对于突变BRAF的锯齿状病变，显著的危险因素是男性、当前吸烟状况、肥胖和息肉病史。我们的研究结果表明，SSP和其他大型右侧锯齿状病变具有独特的分子特征，与CIMP高水平、BRAF突变的结直肠癌相似。(C)2013年AACR。
A subset of aggressive colorectal cancers exhibit BRAF mutation, MLH1 methylation, and a CpG island methylator phenotype (CIMP), but precursors are poorly established. In this study, we determined the status of these markers in colorectal polyps and evaluated associated risk factors. The study included 771 polyp cases and 1,027 controls who were ages 24 to 80 years, part of a group health program, received a colonoscopy from 1998 to 2007, and completed a structured questionnaire assessing risk factors. Following standard pathology review, polyps were assayed for BRAF mutation (V600E) and tested for MLH1 and CIMP methylation, the latter including the genes, CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1. Polytomous logistic regression was used to estimate ORs and 95% confidence intervals for the association between molecularly defined subsets of polyps and potential risk factors. There were 580 conventional adenomas and 419 serrated lesions successfully assayed. For adenomas, the prevalence of each marker was = 10 mm that were in the right-side/cecal regions of the colon. Risk factors for CIMP-high-serrated lesions included Caucasian race, current smoking status, and a history of polyps, whereas for serrated lesions with mutant BRAF, the significant risk factors were male sex, current smoking status, obesity, and a history of polyps. Our results suggest that SSPs and other large, right-sided serrated lesions have a unique molecular profile that is similar to CIMP-high, BRAF-mutated colorectal cancers. (C) 2013 AACR.