PMID- 25017244
OWN - NLM
STAT- MEDLINE
DCOM- 20150731
LR  - 20211021
IS  - 1538-7755 (Electronic)
IS  - 1055-9965 (Print)
IS  - 1055-9965 (Linking)
VI  - 23
IP  - 10
DP  - 2014 Oct
TI  - Reduced insulin-like growth factor I receptor and altered insulin receptor 
      isoform mRNAs in normal mucosa predict colorectal adenoma risk.
PG  - 2093-100
LID - 10.1158/1055-9965.EPI-14-0177 [doi]
AB  - 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.
CI  - (c)2014 American Association for Cancer Research.
FAU - Santoro, M Agostina
AU  - Santoro MA
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina.
FAU - Andres, Sarah F
AU  - Andres SF
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina.
FAU - Galanko, Joseph A
AU  - Galanko JA
AD  - Department of Medicine and Center for Gastrointestinal Biology and Disease, 
      University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
FAU - Sandler, Robert S
AU  - Sandler RS
AD  - Department of Medicine and Center for Gastrointestinal Biology and Disease, 
      University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
FAU - Keku, Temitope O
AU  - Keku TO
AD  - Department of Medicine and Center for Gastrointestinal Biology and Disease, 
      University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
FAU - Lund, P Kay
AU  - Lund PK
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina. empk@med.unc.edu.
LA  - eng
GR  - R01 CA044684/CA/NCI NIH HHS/United States
GR  - P30 DK034987/DK/NIDDK NIH HHS/United States
GR  - CA136887/CA/NCI NIH HHS/United States
GR  - R01 DK040247/DK/NIDDK NIH HHS/United States
GR  - DK040247/DK/NIDDK NIH HHS/United States
GR  - R01 CA136887/CA/NCI NIH HHS/United States
GR  - CA044684/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140713
PL  - United States
TA  - Cancer Epidemiol Biomarkers Prev
JT  - Cancer epidemiology, biomarkers & prevention : a publication of the American 
      Association for Cancer Research, cosponsored by the American Society of 
      Preventive Oncology
JID - 9200608
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Adenoma/*metabolism/pathology
MH  - Apoptosis
MH  - Colorectal Neoplasms/*metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Protein Isoforms
MH  - RNA, Messenger
MH  - Receptor, IGF Type 1/*biosynthesis
MH  - Receptor, Insulin/*biosynthesis
PMC - PMC4201381
MID - NIHMS614074
COIS- Conflict of interests: The authors declared no conflict of interests.
EDAT- 2014/07/16 06:00
MHDA- 2015/08/01 06:00
PMCR- 2015/10/01
CRDT- 2014/07/15 06:00
PHST- 2014/07/15 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/08/01 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - 1055-9965.EPI-14-0177 [pii]
AID - 10.1158/1055-9965.EPI-14-0177 [doi]
PST - ppublish
SO  - Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2093-100. doi: 
      10.1158/1055-9965.EPI-14-0177. Epub 2014 Jul 13.