No Association Between Cyclooxygenase-2 and Uridine Diphosphate Glucuronosyltransferase 1A6 Genetic Polymorphisms and Colon Cancer Risk

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2009 May 14

PMID 19437564

Citations 22

Authors

Cheryl-L Thompson

Sarah-J Plummer

Alona Merkulova

Iona Cheng

Thomas-C Tucker

Graham Casey

Li Li

Affiliations

Soon will be listed here.

Abstract

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.

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References

Hubner R, Muir K, Liu J, Logan R, Grainge M, Armitage N . Genetic variants of UGT1A6 influence risk of colorectal adenoma recurrence. Clin Cancer Res. 2006; 12(21):6585-9. DOI: 10.1158/1078-0432.CCR-06-0903. View

Li L, Plummer S, Thompson C, Tucker T, Casey G . Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk. Clin Cancer Res. 2008; 14(3):633-7. DOI: 10.1158/1078-0432.CCR-07-1211. View

Samowitz W, Wolff R, Curtin K, Sweeney C, Ma K, Andersen K . Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Clin Gastroenterol Hepatol. 2006; 4(7):894-901. DOI: 10.1016/j.cgh.2006.04.021. View

Bosetti C, Gallus S, La Vecchia C . Aspirin and cancer risk: an updated quantitative review to 2005. Cancer Causes Control. 2006; 17(7):871-88. DOI: 10.1007/s10552-006-0033-7. View

Ulrich C, Whitton J, Yu J, Sibert J, Sparks R, Potter J . PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev. 2005; 14(3):616-9. DOI: 10.1158/1055-9965.EPI-04-0510. View

Wiesner G, Platzer P, Buxbaum S, Lewis S, MacMillen M, Olechnowicz J . Testing for colon neoplasia susceptibility variants at the human COX2 locus. J Natl Cancer Inst. 2001; 93(8):635-9. DOI: 10.1093/jnci/93.8.635. View

Williams C, Mann M, DuBois R . The role of cyclooxygenases in inflammation, cancer, and development. Oncogene. 2000; 18(55):7908-16. DOI: 10.1038/sj.onc.1203286. View

Bigler J, Whitton J, Lampe J, Fosdick L, Bostick R, Potter J . CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res. 2001; 61(9):3566-9. View

Goodman J, Bowman E, Chanock S, Alberg A, Harris C . Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Carcinogenesis. 2004; 25(12):2467-72. DOI: 10.1093/carcin/bgh260. View

10.

Shahedi K, Lindstrom S, Zheng S, Wiklund F, Adolfsson J, Sun J . Genetic variation in the COX-2 gene and the association with prostate cancer risk. Int J Cancer. 2006; 119(3):668-72. DOI: 10.1002/ijc.21864. View

11.

Ciotti M, Marrone A, Potter C, Owens I . Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics. 1998; 7(6):485-95. DOI: 10.1097/00008571-199712000-00007. View

12.

Eberhart C, Coffey R, Radhika A, Giardiello F, Ferrenbach S, DuBois R . Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994; 107(4):1183-8. DOI: 10.1016/0016-5085(94)90246-1. View

13.

Chan A, Tranah G, Giovannucci E, Hunter D, Fuchs C . Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma. J Natl Cancer Inst. 2005; 97(6):457-60. DOI: 10.1093/jnci/dji066. View

14.

Siezen C, Bueno-de-Mesquita H, Peeters P, Kram N, van Doeselaar M, van Kranen H . Polymorphisms in the genes involved in the arachidonic acid-pathway, fish consumption and the risk of colorectal cancer. Int J Cancer. 2006; 119(2):297-303. DOI: 10.1002/ijc.21858. View

15.

Potter J . Colorectal cancer: molecules and populations. J Natl Cancer Inst. 1999; 91(11):916-32. DOI: 10.1093/jnci/91.11.916. View

16.

Cox D, Pontes C, Guino E, Navarro M, Osorio A, Canzian F . Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer. Br J Cancer. 2004; 91(2):339-43. PMC: 2409800. DOI: 10.1038/sj.bjc.6601906. View

17.

McGreavey L, Turner F, Smith G, Boylan K, Bishop D, Forman D . No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma. Pharmacogenet Genomics. 2005; 15(10):713-21. DOI: 10.1097/01.fpc.0000174786.85238.63. View