BackgroundThe methylation of DNA is recognized as a key epigenetic mechanism and evidence for its role in the development of several malignancies is accumulating. We evaluated the relationship between global methylation in DNA derived from normal appearing colon mucosal tissue and blood leukocytes, and colorectal adenoma risk.MethodsPatients, aged 40 to 65, scheduled for a screening colonoscopy were recruited. During the colonoscopy, two pinch biopsies of healthy, normal appearing mucosa were obtained from the descending colon. A fasting blood sample was also collected. The methylation status of LINE-1 (long interspersed nuclear element-1) repetitive sequences, as a surrogate measure of global methylation, was quantified in DNA extracted from normal colon mucosa and blood leukocytes. Statistical analysis of the relationship between global DNA methylation and adenoma risk was conducted on 317 participants, 108 subjects with at least one pathologically confirmed adenoma and 209 subjects with a normal colonoscopy.ResultsA statistically significant inverse relationship was observed between LINE-1 methylation in colon tissue DNA and adenoma risk for males and for both sexes combined for the lowest methylation quartile compared to the highest (adjusted ORs = 2.94 and 2.26 respectively). For blood, although the overall pattern of odds ratio estimates was towards an increase in risk for lower methylation quartiles compared to the highest methylation quartile, there were no statistically significant relationships observed. A moderate correlation was found between LINE-1 methylation levels measured in tissue and blood (Pearson correlation 0.36).ConclusionsWe observed that lower levels of LINE-1 DNA methylation in normal appearing background colon mucosa were associated with increased adenoma risk for males, and for both sexes combined. Though these findings provide some support for a relationship between LINE-1 DNA methylation in colon mucosal tissue and adenoma risk, large prospective cohort studies are needed to confirm results. Until such investigations are done, the clinical usefulness of LINE-1 methylation as a biomarker of increased adenoma risk is uncertain. Regardless, this study contributes to a better understanding of the role of global DNA methylation as an early event in CR carcinogenesis with implications for future etiologic research.
Background
Screening sigmoidoscopy is effective in reducing mortality from colorectal cancer. In 2009, Cancer Care Ontario (CCO) launched a nurse-performed screening flexible sigmoidoscopy program at Hotel Dieu Hospital, Kingston, Ontario. Prior to this program, there was a pilot sigmoidoscopy screening program by gastroenterologists in a similar average risk cohort.
Aim
To compare neoplasia detection rates and associated costs of screening sigmoidoscopy performed by nurses and gastroenterologists.
Method
A retrospective chart review was conducted on flexible sigmoidoscopies performed as part of two average risk screening programs performed by gastroenterologists and nurse-endoscopists. Detected polyps were categorized as hyperplastic, low-risk adenomas or high-risk adenomas. Average cost per procedure was estimated based on physician fee for service charges, nurse wage and benefits, physician supervisory fees, pathology costs and administrative expenses.
Results
There were 538 procedures performed by nurses and 174 by physicians. Adenomas were detected in 18% of nurse-performed procedures versus 9% in physician-performed procedures (p=0.003), with the higher adenoma detection rate restricted to low risk adenomas. One cancer was found in the physician group. Seven physicians performed the 174 sigmoidoscopies, with one physician performing the majority. This physician’s adenoma detection rate was 4.5%, whereas detection rate for the remaining physicians combined was 16.5%. Nurses biopsied more polyps per case (0.96 versus 0.18). Average estimated cost per case was greater for nurses ($387.54 versus $309.37).
Conclusion
Well-trained nurse-endoscopists can provide an effective service for colorectal cancer screening, but as currently structured in Ontario, the associated cost is higher for nurse-performed procedures.
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