Abstract
BackgroundConventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Whether features of adenomas could serve as predictors of synchronous CRC is not known. Here, we investigate whether global methylation markers, including LINE-1, differ within adenomas in patients with and without synchronous CRC.MethodsColorectal tubular/tubulovillous adenomatous polyps in the absence (P group, n = 45) and in the presence of synchronous CRC (PC group, n = 32) were identified. Global methylation and demethylation by ELISA for 5-methylcytosine (5-mC) and 5-hydroxymethyl cytosine (5-hmC), respectively, were assessed in polyps and adjacent normal non-neoplastic tissue. LINE-1 hypomethylation was assessed by pyrosequencing of bisulfite-converted DNA as well.ResultsGlobal methylation (5-mC) showed no differences in overall methylation status in the adenomatous polyps in the two groups (5-mC relative to control %, PC group 0.117; P group 0.161, p = 0.148). Global hydroxymethylation 5-hmC was also not significantly different in adenomatous polyps of the PC group than in those of the P group (0.0059 vs 0.0097, p = 0.681). Similarly, global 5-hmC was not different between normal tissues from patients without neoplasia in comparison to those from CRC patients (0.0461 ± 0.080 vs 0.039 ± 0.159, p = 0.215). In contrast, adenomatous polyps of the PC group had lower levels of LINE-1 methylation compared to the adenomas in the P group (53.07 ± 4.5 vs 59.95 ± 5.4, p < 0.001). LINE-1 methylation was also significantly lower in the normal tissue from cancer patients compared to that from patients without any neoplasia (58.07 ± 3.78 vs 71.50 ± 6.47, p < 0.001).ConclusionsLINE-1 hypomethylation of precancerous adenomas correlates with the presence of synchronous CRC. Measurement of DNA hypomethylation levels of colorectal adenomas by LINE-1 could have future implications in approaches to defining CRC risk in screening programs.
Highlights
Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC)
Our findings suggest that long interspersed nuclear elements (LINEs)-1 methylation status of adenomatous polyps or normal tissue obtained during surveillance colonoscopies could more effectively risk-stratify patients for development of synchronous CRC
Similar to Sunami et al, that there was a trend toward hypomethylation in progression from normal tissue in the absence of neoplasia to adenoma to CRC which had the lowest levels of LINE-1 methylation
Summary
Conventional tubular adenomas are frequently detected in patients undergoing average risk screening colonoscopy and are over-represented in patients who will develop colorectal cancer (CRC). Adenoma detection rates (ADR) in patients who undergo screening colonoscopy have incrementally increased over time. Surveillance intervals for repeating follow-up colonoscopy are based on pathology features defining advanced adenomas by the presence of villous histology or high-grade dysplasia, size of polyp, or multiplicity [4, 5]. Even in patients whose initial colonoscopy yields an advanced adenoma, and deemed the high-risk group based on US Multi-Society Task Force (USMTF) recommendations, still the majority of these patients will not have further advanced neoplasia on surveillance colonoscopy [6, 7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
