| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
1 Health Research Center and 2 Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT; 3 Kaiser Permanente Medical Research Program, Oakland, CA; 4 University of California at Irvine, Irvine, CA
Requests for reprints: Martha L. Slattery, Health Research Center, University of Utah, 375 Chipeta Way, Suite A, Salt Lake City, UT 84108. Phone: (801) 585-6955; Fax: (801) 581-3623. E-mail: mslatter{at}hrc.utah.edu
Introduction: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce risk of colorectal cancer. Although inhibition of cyclooxygenase (COX)-2 is generally thought to be the relevant mechanism, aspirin-like drugs apparently are involved in other pathways and mechanisms. We explore the associations between aspirin/NSAIDs, the insulin-related pathway, and the risk of colorectal cancer. Methods: Genetic polymorphisms of five genes identified as being involved in an insulin-related pathway were genotyped using data collected in a case-control study of 1346 incident colon cancer cases and 1544 population-based controls and 952 incident rectal cancer cases and 1205 controls. Genotypes assessed were the 3' untranslated region poly(A) and the intron 8 BsmI polymorphisms of the VDR gene, a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide –202 of the IGFBP3, the Gly972Arg polymorphism of the IRS1 gene, and the Gly1057Asp polymorphism of the IRS2 gene. Results: Use of aspirin and NSAIDs was associated with a decreased risk of colorectal cancer, with slightly greater protection from NSAIDs than aspirin for rectal cancer. We observed a significant interaction between IRS1 genotype and aspirin/NSAIDs use and risk of colorectal cancer. Relative to the GR/RR IRS1 genotype, a protective effect from the GG IRS1 genotype was seen in those who did not use NSAIDs; use of NSAIDs was protective for all genotypes. These associations were especially strong for those diagnosed prior to age 65 (P interaction = 0.0006). We also observed a significant interaction between aspirin/NSAIDs use and the VDR gene. Having the SS or BB VDR genotypes reduced risk of colorectal cancer among non-aspirin/NSAID users; however, aspirin/NSAIDs reduced risk for all VDR genotypes. Conclusions: These data support the protective effect of aspirin and NSAIDs on colorectal cancer risk. In addition, the observed interactions for aspirin/NSAIDs and IRS1 and VDR genotypes suggest that mechanisms other than COX-2 inhibition may be contributing to the protective effect of aspirin and NSAIDs on colorectal cancer risk.
This article has been cited by other articles:
|
|
 |
|
  M. L. Slattery, A. R. Folsom, R. Wolff, J. Herrick, B. J. Caan, and J. D. Potter Transcription Factor 7-like 2 Polymorphism and Colon Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 978 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dube, A. Rostom, G. Lewin, A. Tsertsvadze, N. Barrowman, C. Code, M. Sampson, and D. Moher The Use of Aspirin for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force Ann Intern Med, March 6, 2007; 146(5): 365 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rostom, C. Dube, G. Lewin, A. Tsertsvadze, N. Barrowman, C. Code, M. Sampson, and D. Moher Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force Ann Intern Med, March 6, 2007; 146(5): 376 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sweeney, K. Curtin, M. A. Murtaugh, B. J. Caan, J. D. Potter, and M. L. Slattery Haplotype analysis of common vitamin d receptor variants and colon and rectal cancers. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 744 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sweeney, M. A. Murtaugh, K. B. Baumgartner, T. Byers, A. R. Giuliano, J. S. Herrick, R. Wolff, B. J. Caan, and M. L. Slattery Insulin-Like Growth Factor Pathway Polymorphisms Associated with Body Size in Hispanic and Non-Hispanic White Women Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1802 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. McCarthy, X. Li, and C. J. Sinal Vitamin D Receptor-dependent Regulation of Colon Multidrug Resistance-associated Protein 3 Gene Expression by Bile Acids J. Biol. Chem., June 17, 2005; 280(24): 23232 - 23242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Murtaugh, K.-n. Ma, B. J. Caan, C. Sweeney, R. Wolff, W. S. Samowitz, J. D. Potter, and M. L. Slattery Interactions of Peroxisome Proliferator-Activated Receptor {gamma} and Diet in Etiology of Colorectal Cancer Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1224 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Kemp, C. Thirlwell, O. Sieber, A. Silver, and I. Tomlinson An update on the genetics of colorectal cancer Hum. Mol. Genet., October 1, 2004; 13(suppl_2): R177 - R185. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
