Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.

Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.

Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.

Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD– to be further tested in prospective studies.

背景与目的：结肠受累的炎症性肠病（IBD）增加了结直肠癌的风险。然而，很难区分IBD患者中IBD相关性和散发性异型增生。一些数据支持异常DNA甲基化在IBD相关癌变中的重要性。我们旨在定义IBD诊断后患有结肠癌或发育异常的患者的甲基化模式。

方法：多中心横断面研究-包括来自9例IBD相关性不典型增生/癌症和26例IBD和偶发性不典型增生/癌症的结肠黏膜伴/不伴异型的样本。通过甲基化特异性多重连接依赖探针扩增研究了67个基因的启动子区域中CpG岛的甲基化模式。

结果： IBD诊断的平均年龄为42±16岁；发育异常的诊断为56±14岁。二十九名患者患有溃疡性结肠炎。25例患者在内窥镜检查中至少有1个病灶样腺瘤样病变，4个至少1个非腺瘤样病变，3例癌变，3例扁平粘膜增生。没有患者同时患有腺瘤样和非腺瘤样病变。IBD相关病变的患者在IBD诊断时（p  = .003）和不典型增生/癌症诊断时（p  = .039）明显年轻。IGF2，RARB，ESR1，CHFR，CDH13，WT1，GATA5，WIF1基因的启动子甲基化与发育异常/癌症显着相关；MSH6，TIMP3的甲基化与IBD相关的不典型增生/癌症显着相关。MSH6，MSH3，RUNX3，CRABP1，TP73，RARB，CDH13，PAX5，WT1，THBS1，TP53，SFRP1，WIF1，APAF1， BCL2基因的启动子甲基化与活性IBD显着相关。

结论：甲基化分析，即MSH6，可能有助于IBD发育异常病变的分类，有待于前瞻性研究进一步检验。