Reduced insulin-like growth factor I receptor and altered insulin receptor isoform mRNAs in normal mucosa predict colorectal adenoma risk
| Autor: | Joseph A. Galanko, Robert S. Sandler, Sarah F. Andres, M. Agostina Santoro, P. Kay Lund, Temitope O. Keku |
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| Rok vydání: | 2014 |
| Předmět: |
Adenoma
Male medicine.medical_specialty Epidemiology medicine.medical_treatment Apoptosis Enzyme-Linked Immunosorbent Assay Colorectal adenoma Biology Polymerase Chain Reaction Article Receptor IGF Type 1 Insulin resistance Internal medicine medicine Hyperinsulinemia In Situ Nick-End Labeling Humans Protein Isoforms RNA Messenger TUNEL assay Insulin Cancer Middle Aged medicine.disease Receptor Insulin Insulin receptor Endocrinology Oncology biology.protein Female Colorectal Neoplasms |
| Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 23(10) |
| ISSN: | 1538-7755 |
| Popis: | Background: Hyperinsulinemia resulting from obesity and insulin resistance is associated with increased risk of many cancers, but the biology underlying this risk is unclear. We hypothesized that increased mRNA levels of the insulin-like growth factor I receptor (IGFIR) versus the insulin receptor (IR) or elevated ratio of IR-A:IR-B isoforms in normal rectal mucosa would predict adenoma risk, particularly in individuals with high body mass index (BMI) or plasma insulin. Methods: Biopsies from normal rectal mucosa were obtained from consenting patients undergoing routine colonoscopy at University of North Carolina Hospitals (Chapel Hill, NC). Subjects with colorectal adenomas were classified as cases (n = 100) and were matched to adenoma-free controls (n = 98) based on age, sex, and BMI. IGFIR and IR mRNA levels were assessed by qRT-PCR, and IR-A:IR-B mRNA ratios by standard PCR. Plasma insulin and crypt apoptosis were measured by ELISA and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), respectively. Logistic regression models examined relationships between receptor mRNAs, BMI, plasma insulin, and adenoma risk. Results: Unexpectedly, cases were significantly more likely to have lower IGFIR mRNA levels than controls. No overall differences in total IR mRNA or IR-A:IR-B ratios were observed between cases and controls. Interestingly, in patients with high plasma insulin, increased IR-A:IR-B ratio was associated with increased likelihood of having adenomas. Conclusions: Our work shows novel findings that reduced IGFIR mRNA and, during high plasma insulin, increased IR-A:IR-B ratios in normal rectal mucosa are associated with colorectal adenoma risk. Impact: Our work provides evidence supporting a link between IGFIR and IR isoform expression levels and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev; 23(10); 2093–100. ©2014 AACR. |
| Databáze: | OpenAIRE |
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