Insulin Resistance, Apoptosis, and Colorectal Adenoma Risk
Compelling evidence from epidemiologic studies indicates that elevated circulating insulin-like growth factor (IGF)-I, insulin resistance, and associated complications, such as elevated fasting plasma insulin, glucose and free fatty acids, glucose intolerance, increased body mass index, and visceral...
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Veröffentlicht in: | Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2005-09, Vol.14 (9), p.2076-2081 |
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Zusammenfassung: | Compelling evidence from epidemiologic studies indicates that elevated circulating insulin-like growth factor (IGF)-I, insulin
resistance, and associated complications, such as elevated fasting plasma insulin, glucose and free fatty acids, glucose intolerance,
increased body mass index, and visceral adiposity, are linked with increased risk of colorectal cancer. However, the role
of insulin and markers of glucose control in the development of adenomas, precursors to colorectal cancer, has not been fully
explored. We evaluated the relationship between plasma insulin, glucose, IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), apoptosis,
and colorectal adenomas in a case-control study. Participants were drawn from consenting patients undergoing colonoscopy at
the University of North Carolina hospitals (Chapel Hill, NC). Participants were classified as cases or controls based on whether
they had one or more colorectal adenomatous polyps. Fasting plasma insulin, IGF-I, IGF-II, and IGFBP-3 levels were assessed
by ELISA. Glucose was measured by glucose hexokinase assay. Apoptosis was assessed by morphology on H&E-stained sections.
Dietary and lifestyle information were obtained by telephone interview. Logistic regression was used to examine the association
between adenoma status and insulin-IGF markers. Adenoma cases ( n = 239) and adenoma-free controls ( n = 517) provided rectal biopsies and/or blood samples and interview data. Consistent with prior findings, cases were more
likely to be males, older, have higher waist-to-hip ratio, lower calcium intake, lower apoptosis, and less likely to report
nonsteroidal anti-inflammatory drug use. Those in the highest quartile of insulin (adjusted odds ratio, 2.2; 95% confidence
interval, 1.1-4.2) and glucose (adjusted odds ratio, 1.8; 95% confidence interval, 0.9-3.6) were more likely to have an adenoma
compared with the lowest quartile. Similarly, subjects in the highest two quartiles of insulin were more likely to be in the
lowest two quartiles of apoptosis. Overall, there were no significant differences between mean circulating levels of glucose,
IGF-I, IGF-II, and IGFBP-3 among cases and controls and no association between these variables and apoptosis. The results
provide novel evidence that elevated insulin and glucose are associated with increased adenoma risk and decreased apoptosis
in normal rectal mucosa. These findings suggest that insulin may act early in the adenoma-carcinoma sequence to promote the
development |
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ISSN: | 1055-9965 1538-7755 |
DOI: | 10.1158/1055-9965.EPI-05-0239 |