DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer

Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age

“…It is likely that this inter-individual variability is related to subject age as we noted a direct correlation between ESR1 promoter methylation and age, consistent with prior reports. 1,32,33 These results have obvious implications regarding the development of biomarker assays based on methylated DNA.…”

“…2,31 Aberrant methylation of CDKN2A, meanwhile, is frequently seen in neoplastic lesions of the colon but not in uninvolved normal colon mucosa. 32 The estrogen receptor gene, ESR1, has been shown to exhibit increasing promoter methylation that is associated with colon neoplasia as well as with increasing age. 1,32,33 We confirmed that LINE-1 and SAT-α show a relatively high level of DNA methylation as expected in normal colon mucosa, ranging from approximately 70-80% in the loci we examined.…”

“…32 The estrogen receptor gene, ESR1, has been shown to exhibit increasing promoter methylation that is associated with colon neoplasia as well as with increasing age. 1,32,33 We confirmed that LINE-1 and SAT-α show a relatively high level of DNA methylation as expected in normal colon mucosa, ranging from approximately 70-80% in the loci we examined. The degree of methylation did not differ substantially between various colon segments or between the eight normal study subjects.…”

The Impact of Colonoscopy on Colorectal Cancer Incidence and Mortality

“…This carcinogenic pathway may also be associated with more rapid transformation to cancer (Sawhney et al, 2006;Arain et al, 2008). Other studies also showed significantly higher MLH1 and MGMT promoter methylation in the normal proximal colon in older women (Worthley et al, 2010;Menigatti et al, 2009) and K-ras mutations in 80% of hyperplastic polyps in women, compared to 36% in men (Otori et al, 1997), suggesting the intriguing possibility that the epigenetic signatures of cancers may have sex-and segment-specific, early-stage and normal-tissue counterparts. The failure to detect proximal lesions may also be caused by incomplete colonoscopy, which in turn is associated with patient-related factors such as prior history of pelvic or abdominal surgery (i.e., hysterectomy, gastrectomy), old age and inadequate bowel prep (Lee et al, 2006).…”

DNA Methylation and Histone Deacetylation: Interplay and Combined Therapy in Cancer

“…Recent studies suggest that methylation patterns can be different in different cancer types and tumor stages (Wermann et al, 2010). Epigenetic analysis of large gene panels and genomewide screening of DNA methylation levels discovered that overall methylation patterns can be used as biomarkers for cancer risk and/or tumor type (Kondo & Issa, 2010,Figueroa et al, 2010,Hawes et al, 2010,Worthley et al, 2010. Cancer-specific differentially methylated regions (cDMRs) were identified; methylation variation within these cDMRs distinguishes various cancers from normal tissue, with intermediate variation in adenomas (Hansen et al, 2011).…”