2010
DOI: 10.1158/1940-6207.capr-10-0047
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Association between Folate Levels and CpG Island Hypermethylation in Normal Colorectal Mucosa

Abstract: Gene-specific promoter methylation of several genes occurs in aging normal tissues and may predispose to tumorigenesis. In the present study, we investigate the association of blood folate levels and dietary and lifestyle factors with CpG island (CGI) methylation in normal colorectal mucosa. Subjects were enrolled in a multicenter chemoprevention trial of aspirin or folic acid for the prevention of large bowel adenomas. We collected 1,000 biopsy specimens from 389 patients, 501 samples from the right colon and… Show more

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Cited by 109 publications
(110 citation statements)
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References 48 publications
(72 reference statements)
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“…The bias of CIMPþ and MSI cancers to the right colon (43) and their increased synchronicity (44) would be consistent with a field defect, perhaps involving changes to DNA methylation or folate profiles. Indeed, higher erythrocyte folate has been associated with increased CpG island methylation in normal colonic mucosa (45), whereas altered folate distribution has been seen in CIMPþ cancers (46). In this study, both CIMPþ and MSI tumors were present at frequencies (18.2% and 20.4%, respectively) broadly consistent with previous reports.…”
Section: Discussionmentioning
confidence: 99%
“…The bias of CIMPþ and MSI cancers to the right colon (43) and their increased synchronicity (44) would be consistent with a field defect, perhaps involving changes to DNA methylation or folate profiles. Indeed, higher erythrocyte folate has been associated with increased CpG island methylation in normal colonic mucosa (45), whereas altered folate distribution has been seen in CIMPþ cancers (46). In this study, both CIMPþ and MSI tumors were present at frequencies (18.2% and 20.4%, respectively) broadly consistent with previous reports.…”
Section: Discussionmentioning
confidence: 99%
“…Taking into consideration both measured and unmeasured risk factors/genetic susceptibilities, molecular information derived from histologically normal mucosae has been extensively investigated, such as the field effects of oral leukoplakia, Barrett's esophagus (39), and colon neoplasm (40,41). Mutations of p53 or p53 oncoprotein are relatively late events in carcinogenesis (42,43), so, despite their biological plausibility as cancer predictors, they are insufficient for risk assessments for SCC in the UADT.…”
Section: Discussionmentioning
confidence: 99%
“…Folate supplementation has come under fire recently, with some studies raising safety concerns by showing an association with an increased incidence of and/or mortality from various cancers (18). Furthermore, laboratory research has linked high levels of folate with accelerated age-related DNA methylation (19), leading one to wonder whether diet could have had an influence on the constitutional methylation as reported by Wong et al (3). Indeed, folate (and diet in general) may be just the tip of an iceberg of epigenetic modulators.…”
mentioning
confidence: 99%