Brief Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 14, 2009; 15(18): 2240-2244
Published online May 14, 2009. doi: 10.3748/wjg.15.2240
No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk
Cheryl L Thompson, Sarah J Plummer, Alona Merkulova, Iona Cheng, Thomas C Tucker, Graham Casey, Li Li
Cheryl L Thompson, Li Li, Departments of Family Medicine and Epidemiology and Biostatistics, Case Center for Transdisciplinary Research on Energetics and Cancer, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106-7136, United States
Sarah J Plummer, Graham Casey, Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033-1006, United States
Alona Merkulova, Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, OH 44195-0001, United States
Iona Cheng, Department of Epidemiology and Biostatistics and Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143-0644, United States
Thomas C Tucker, Markey Cancer Center, University of Kentucky, Lexington, KY 40504-3381, United States
Author contributions: Thompson CL performed the statistical analyses, assisted with the subject recruitment and data collection and drafted the manuscript; Plummer SJ conducted some of the genotyping and assisted with the manuscript preparation; Merkulova A performed some of the genotyping; Tucker TC assisted with patient referrals and recruitment; Casey G coordinated the lab work and assisted with manuscript preparation; Li L led the study design and data collection and assisted with the manuscript preparation; Cheng I selected the SNPs for inclusion in the study and reviewed the manuscript.
Correspondence to: Li Li, MD, PhD, Department of Family Medicine, Research Division, Case Western Reserve University, 11001 Cedar Ave., Suite 306, Cleveland, Ohio 44106-7136, United States.
Telephone: +1-216-3685437
Fax: +1-216-3684348
Received: January 10, 2009
Revised: March 21, 2009
Accepted: March 28, 2009
Published online: May 14, 2009

AIM: To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with risk of colon cancer.

METHODS: NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly, enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms (SNPs) in the COX2 and UGT1A6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.

RESULTS: No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk (P > 0.05), and we did not observe that these variants modify the protective effect of NSAIDs (P > 0.05). We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.

CONCLUSION: Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.

Keywords: Uridine diphosphate glucuronosyltransferase 1A6, Cyclooxygenase-2, Non-steroidal anti-inflammatory drugs, Colon cancer, Genetic association studies, Single nucleotide polymorphisms