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Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors

Authors: Randall E Harris, Joanne Beebe-Donk, Galal A Alshafie

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Epidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade.

Methods

We conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 326 incident colon cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 652 controls with no history of cancer and matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and colon cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR) and 95% confidence intervals.

Results

Results showed significant risk reductions for selective COX-2 inhibitors (OR = 0.31, 95% CI = 0.16–0.57), regular aspirin (OR = 0.33, 95% CI = 0.20–0.56), and ibuprofen or naproxen (0.28, 95% CI = 0.15–0.54). Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no significant change in the risk of colon cancer.

Conclusion

These results suggest that both non-selective and selective COX-2 inhibitors produce significant reductions in the risk of colon cancer, underscoring their strong potential for colon cancer chemoprevention.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun JM: Cancer statistics, 2007. CA Cancer J Clin. 2007, 57: 43-66.CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun JM: Cancer statistics, 2007. CA Cancer J Clin. 2007, 57: 43-66.CrossRefPubMed
2.
go back to reference Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, Schrag D, Jamison PM, Jemal A, Wu XC, Friedman C, Harlan L, Warren J, Anderson RN, Pickle LW: Annual report to the nation on the status of cancer, 1975-featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005, 97 (19): 1407-1427.CrossRefPubMed Edwards BK, Brown ML, Wingo PA, Howe HL, Ward E, Ries LA, Schrag D, Jamison PM, Jemal A, Wu XC, Friedman C, Harlan L, Warren J, Anderson RN, Pickle LW: Annual report to the nation on the status of cancer, 1975-featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005, 97 (19): 1407-1427.CrossRefPubMed
3.
4.
go back to reference Harris RE, Beebe-Donk J, Doss H, Burr-Doss D: Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (Review). Oncol Rep. 2005, 13 (4): 559-583.PubMed Harris RE, Beebe-Donk J, Doss H, Burr-Doss D: Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (Review). Oncol Rep. 2005, 13 (4): 559-583.PubMed
5.
6.
7.
go back to reference Schlesselman JJ: Case Control Studies. 1982, Oxford University Press, New York Schlesselman JJ: Case Control Studies. 1982, Oxford University Press, New York
8.
go back to reference Harrell F: Logistic Regression Procedure. 2005, Statistical Analysis System (SAS) Harrell F: Logistic Regression Procedure. 2005, Statistical Analysis System (SAS)
9.
go back to reference Rahme E, Barkun AN, Goubouti Y, Bardolu M: The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology. 2003, 125 (2): 404-412.CrossRefPubMed Rahme E, Barkun AN, Goubouti Y, Bardolu M: The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence. Gastroenterology. 2003, 125 (2): 404-412.CrossRefPubMed
10.
go back to reference Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature. 1971, 231: 323-235. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature. 1971, 231: 323-235.
11.
go back to reference Herschman HR: Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer and Metas Rev. 1994, 13: 241-256.CrossRef Herschman HR: Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer and Metas Rev. 1994, 13: 241-256.CrossRef
13.
go back to reference Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, Dubois RN: Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenoma and adenocarcinoma. Gastroenterology. 1994, 107: 1183-1188.CrossRefPubMed Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, Dubois RN: Up-regulation of cyclooxygenase-2 gene expression in human colorectal adenoma and adenocarcinoma. Gastroenterology. 1994, 107: 1183-1188.CrossRefPubMed
14.
go back to reference Sano H, Kawahito Y, Wilder R, Hashiramotot A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T: Expression of cylcooxygenase-1 and -2 in colorectal cancer. Cancer Res. 1995, 55: 3785-3789.PubMed Sano H, Kawahito Y, Wilder R, Hashiramotot A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T: Expression of cylcooxygenase-1 and -2 in colorectal cancer. Cancer Res. 1995, 55: 3785-3789.PubMed
15.
go back to reference Masferrer JL, Leahy KM, Koki AT, Aweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000, 60 (5): 1306-1311.PubMed Masferrer JL, Leahy KM, Koki AT, Aweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000, 60 (5): 1306-1311.PubMed
16.
go back to reference Reddy BS, Chinthalapally RV: Role of synthetic and naturally occurring cyclooxygenase inhibitors in colon cancer prevention. COX-2 Blockade in Cancer Prevention and Therapy. Edited by: Harris RE. 2002, Humana Press, Totowa, NJ, 71-83.CrossRef Reddy BS, Chinthalapally RV: Role of synthetic and naturally occurring cyclooxygenase inhibitors in colon cancer prevention. COX-2 Blockade in Cancer Prevention and Therapy. Edited by: Harris RE. 2002, Humana Press, Totowa, NJ, 71-83.CrossRef
17.
go back to reference Reddy BS: Strategies for colon cancer prevention: combination of chemopreventive agents. Subcell Biochem. 2007, 42: 213-25. ReviewCrossRefPubMed Reddy BS: Strategies for colon cancer prevention: combination of chemopreventive agents. Subcell Biochem. 2007, 42: 213-25. ReviewCrossRefPubMed
18.
go back to reference Harris RE: Cyclooxygenase-2 (COX-2) and the inflammogenesis of cancer. Subcell Biochem. 2007, 42: 93-126. ReviewCrossRefPubMed Harris RE: Cyclooxygenase-2 (COX-2) and the inflammogenesis of cancer. Subcell Biochem. 2007, 42: 93-126. ReviewCrossRefPubMed
19.
go back to reference Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET, APC Study Investigators: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006, 355 (9): 873-884.CrossRefPubMed Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET, APC Study Investigators: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006, 355 (9): 873-884.CrossRefPubMed
20.
go back to reference Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B, PreSAP Trial Investigators: Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006, 355 (9): 885-895.CrossRefPubMed Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B, PreSAP Trial Investigators: Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006, 355 (9): 885-895.CrossRefPubMed
21.
go back to reference Kashfi K, Rigas B: Non-COX-2 targets and cancer: expanding the molecular target repertoire of chemoprevention. Biochem Pharmacol. 2005, 70 (7): 969-986.CrossRefPubMed Kashfi K, Rigas B: Non-COX-2 targets and cancer: expanding the molecular target repertoire of chemoprevention. Biochem Pharmacol. 2005, 70 (7): 969-986.CrossRefPubMed
22.
go back to reference Grosch S, Maier TJ, Schiffmann S, Geisslinger G: Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006, 98 (11): 736-747.CrossRefPubMed Grosch S, Maier TJ, Schiffmann S, Geisslinger G: Cyclooxygenase-2 (COX-2)-independent anticarcinogenic effects of selective COX-2 inhibitors. J Natl Cancer Inst. 2006, 98 (11): 736-747.CrossRefPubMed
23.
go back to reference Mukherjee D, Nissen SE, Topol EJ: Risk of cardiovascular events associated with selective COX-2 inhibitors. J Am Med Assoc. 2001, 286 (8): 954-959.CrossRef Mukherjee D, Nissen SE, Topol EJ: Risk of cardiovascular events associated with selective COX-2 inhibitors. J Am Med Assoc. 2001, 286 (8): 954-959.CrossRef
24.
go back to reference Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005, 352 (11): 1092-1102.CrossRefPubMed Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005, 352 (11): 1092-1102.CrossRefPubMed
25.
go back to reference Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005, 352 (11): 1071-1080.CrossRefPubMed Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005, 352 (11): 1071-1080.CrossRefPubMed
27.
go back to reference White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, Geis GS, Lefkowith JB: Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol. 2002, 89 (4): 425-430.CrossRefPubMed White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verburg KM, Geis GS, Lefkowith JB: Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol. 2002, 89 (4): 425-430.CrossRefPubMed
28.
go back to reference White WB, Faich G, Borer JS, Makuch RW: Cardiovascular thrombotic events in arthritis trials of the cyclooxygenase-2 inhibitor, celecoxib. Am J Cardiol. 2003, 92 (4): 411-418.CrossRefPubMed White WB, Faich G, Borer JS, Makuch RW: Cardiovascular thrombotic events in arthritis trials of the cyclooxygenase-2 inhibitor, celecoxib. Am J Cardiol. 2003, 92 (4): 411-418.CrossRefPubMed
29.
go back to reference White WB, West CR, Borer JS, Gorelick PB, Lavange L, Pan SX, Weiner E, Verburg KM: Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol. 2007, 99 (1): 91-98.CrossRefPubMed White WB, West CR, Borer JS, Gorelick PB, Lavange L, Pan SX, Weiner E, Verburg KM: Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol. 2007, 99 (1): 91-98.CrossRefPubMed
Metadata
Title
Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors
Authors
Randall E Harris
Joanne Beebe-Donk
Galal A Alshafie
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-237

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