Grant Details
| Grant Number: | 5R01CA136726-04 Interpret this number |
| Primary Investigator: | Li, Li |
| Organization: | Case Western Reserve University |
| Project Title: | Obesity-Related Insulin Resistance Signaling Pathway Factors and Colon Cancer |
| Fiscal Year: | 2012 |
Abstract
Project Summary Obesity is now established as a potential cause for colon cancer. While the underlying mechanisms mediating the obesity-colon cancer link are not well understood, increasing evidence supports that Insulin resistance resulting from long-term energy imbalance and subsequent perturbation of metabolic homeostasis and insulin signaling pathways form the core of obesity-related colon carcinogenesis. Genetic variations within genes in key insulin and growth factor signaling pathways may, or in combination with obesity, drive the development of colon cancer, but have been little studied. The fact that obesity is escalating as an epidemic worldwide makes the exploration of the mechanistic connections between obesity and colon cancer a pressing public health and research priority. Therefore, we propose a genetic epidemiologic study of the relation of colon cancer with obesity and candidate genes in four critical insulin and related growth factor signaling pathways: 1) phosphatidylinositol-3 Kinase/protein kinase B (PI3K/AKT) signaling cascade; 2) AMP-activated protein kinase (AMPK) pathway; 3) mitogen-activated protein (MAP) kinase pathway; and 4) peroxisome proliferators-activated receptors (PPARs). Each of these pathways plays an important role linking increased adiposity to colon carcinogenesis and model systems indicate that crosstalk occurs among them. We will use both conventional statistical approaches and a novel hierarchical model to comprehensively evaluate obesity and adult weight gain, candidate gene polymorphisms and haplotypes, and their potential joint and interactive effects on colon cancer. The unifying theme of this proposal is that obesity and candidate gene variants within these pathways may act alone or jointly to drive colon carcinogenesis. This study builds upon an ongoing population-based case-control study where epidemiologic data and DNA samples from 1,250 incident colon cancer cases and 1,500 population controls has already being collected. This relatively large study population will be readily available and allow us to dissect complex gene-gene and gene-obesity interactions to gain in- depth understanding of mechanistic link between obesity and colon carcinogenesis.
Publications
Concentrations of arsenic, chromium, and nickel in toenail samples from Appalachian Kentucky residents.
Authors: Johnson N, Shelton BJ, Hopenhayn C, Tucker TT, Unrine JM, Huang B, Christian W, Zhang Z, Shi X, Li L
Source: J Environ Pathol Toxicol Oncol, 2011;30(3), p. 213-23.
PMID: 22126614
Related Citations
Grant Numbers:
| NCI NIH HHS - R01CA136726 |
MeSH Terms:
Insulin resistance, central obesity, and risk of colorectal adenomas.
Authors: Ortiz AP, Thompson CL, Chak A, Berger NA, Li L
Source: Cancer, 2012 Apr 1;118(7), p. 1774-81.
EPub date: 2011 Aug 25.
PMID: 22009143
Related Citations
Grant Numbers:
| NCI NIH HHS - U54 CA-116867 | NCI NIH HHS - 5R25CA094186-08 | NCRR NIH HHS - G12RR03051 |
| NCI NIH HHS - U54CA96297 | NCI NIH HHS - R01 CA136726-01A1 | NCI NIH HHS - R01 CA136726 |
MeSH Terms:
| Waist-Hip Ratio | Risk Factors | Humans |
| Middle Aged | Insulin Resistance | Adenoma |
| Male | Female | Colorectal Neoplasms |
| Obesity, Abdominal | Blood Glucose |
Racial differences in measures of obesity and risk of colon adenoma.
Authors: Thompson CL, Berger NA, Chak A, Li L
Source: Obesity (Silver Spring), 2012 Mar;20(3), p. 673-7.
EPub date: 2011 Oct 13.
PMID: 21996657
Related Citations
Grant Numbers:
| NCI NIH HHS - U54 CA116867 | NCRR NIH HHS - UL1 RR024989 | NCI NIH HHS - K07 CA136758 |
| NCI NIH HHS - K22 CA120545 | NCI NIH HHS - P30 CA043703 | NCI NIH HHS - R01 CA136726 |
MeSH Terms:
FTO polymorphisms are associated with adult body mass index (BMI) and colorectal adenomas in African-Americans.
Authors: Nock NL, Plummer SJ, Thompson CL, Casey G, Li L
Source: Carcinogenesis, 2011 May;32(5), p. 748-56.
EPub date: 2011 Feb 11.
PMID: 21317302
Related Citations
Grant Numbers:
| NCI NIH HHS - K07CA129162 | NCI NIH HHS - R01CA136726 | NCI NIH HHS - U54CA116867 |
MeSH Terms:
Short duration of sleep increases risk of colorectal adenoma.
Authors: Thompson CL, Larkin EK, Patel S, Berger NA, Redline S, Li L
Source: Cancer, 2011 Feb 15;117(4), p. 841-7.
EPub date: 2010 Oct 8.
PMID: 20936662
Related Citations
Grant Numbers:
| NCI NIH HHS - U54 CA116867 | NCRR NIH HHS - KL2 RR024990 | NCI NIH HHS - K22 CA120545-03 |
| NCI NIH HHS - K07 CA136758 | NCI NIH HHS - K22 CA120545 | NCI NIH HHS - R01 CA136726 |
| NCI NIH HHS - R01 CA136726-02 |
MeSH Terms:
| Sleep Apnea Syndromes | Questionnaires | Sleep Disorders, Circadian Rhythm |
| Humans | Sleep Deprivation | Prospective Studies |
| Risk Factors | Sleep | Middle Aged |
| Adenoma | Colorectal Neoplasms | Female |
| Male |
Interleukin-22 genetic polymorphisms and risk of colon cancer.
Authors: Thompson CL, Plummer SJ, Tucker TC, Casey G, Li L
Source: Cancer Causes Control, 2010 Aug;21(8), p. 1165-70.
EPub date: 2010 Mar 26.
PMID: 20339910
Related Citations
Grant Numbers:
| NCI NIH HHS - U54 CA116867 | NCI NIH HHS - R25 CA094186 | NCI NIH HHS - K07 CA136758 |
| NCI NIH HHS - K22 CA120545 | NCI NIH HHS - R01 CA136726 |
MeSH Terms:
| Genetic Variation | Polymorphism, Single Nucleotide | Humans |
| Interleukins | Genotype | Life Style |
| Haplotypes | Risk Factors | Case-Control Studies |
| Middle Aged | Colonic Neoplasms | Female |
| Male |
