No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk |
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Authors: | Cheryl L Thompson Sarah J Plummer Alona Merkulova Iona Cheng Thomas C Tucker Graham Casey Li Li |
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Institution: | 1. 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 2. Department of Preventive Medicine,University of Southern California,Los Angeles,CA 90033-1006,United States 3. Department of Cancer Biology,Cleveland Clinic Foundation,Cleveland,OH 44195-0001,United States 4. Department of Epidemiology and Biostatistics and Institute for Human Genetics,University of California San Francisco,San Francisco,CA 94143-0644,United States 5. Markey Cancer Center,University of Kentucky,Lexington,KY 40504-3381,United States |
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Abstract: | AIM: To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) genes and nonsteroidal 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. |
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Keywords: | Uridine diphosphate glucuronosyltransferase 1A6 Cyclooxygenase-2 Non-steroidal anti-inflammatory drugs Colon cancer Genetic association studies Single nucleotide polymorphisms |
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