Cyclooxygenase-2 Inhibitors in Colorectal Cancer Prevention: Counterpoint

Jankowski, Janusz; Hunt, Richard

doi:10.1158/1055-9965.epi-07-0710

Cited by 36 publications

(17 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hoffmeister et al (52) concluded in their review that few studies have specifically considered NSAIDs and colorectal cancer in the elderly, and two of four studies that did include older people showed a risk reduction similar to that of other age groups; the review by Flossman and Rothwell et al (15) concluded no difference of effect by age group. However, in a trial of a selective COX-2 inhibitor, the greatest suppression of adenomas and colorectal cancers was detected among subjects > 70 years old (53,54). Whether and how lifestyle and biologic changes related to aging (e.g., increased gene hyper-methylation, decreased calcium absorption) contribute to age-related modification of NSAIDs protective action remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Polyps in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Johnson

Hayes

Schoen

et al. 2010

American Journal of Gastroenterology

View full text Add to dashboard Cite

OBJECTIVES Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in animal and human studies to reduce risk for colorectal cancer and adenomatous polyps, but risk modification for subgroups of the population and effects on hyperplastic polyps have been less studied. METHODS Data on recent use of two frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline from participants aged 55–74 years in the 10 centers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to the intervention arm of the trial received a flexible sigmoidoscopy during a baseline examination. Follow-up of detected polyps was accomplished outside the Trial setting and relevant records were sought and abstracted. Cases (n = 4, 017) included subjects with a biopsy-proven polyp in the left side of the colon (descending colon, sigmoid, and rectum) detected as a consequence of PLCO screening; controls (n = 38, 396) were subjects with no left-sided colon polyp. RESULTS Regular use of aspirin (≥ 4 times/month) in the past year was inversely associated with hyperplastic polyps (odds ratios (OR) = 0.8, 95% confidence interval (CI) = 0.7–0.9), adenomatous polyps (OR = 0.8, 95% CI = 0.8–0.9), and advanced adenomas (OR = 0.8, 95% CI = 0.7–0.9). As frequency of aspirin use increased, the prevalence of polyps decreased significantly for each histological classification (P for trend ≤0.0004). Similar patterns were found for adenomas and ibuprofen. Overall protection was consistent in both the descending colon or sigmoid and the rectum, but more evident in males. In males, the OR for heavy use of combined aspirin and ibuprofen (≥ 2 times/day) was 0.6 (95% CI = 0.5–0.8), as opposed to 0.9 (95% CI = 0.8–1.1) in females. The protective effects of NSAIDs for females were apparent only among those with body mass index (BMI) < 25 (OR = 0.8, 95% CI = 0.7–1.0 for regular use of NSAIDs; P interaction = 0.04). We also found a slightly stronger protection of NSAIDs in the 70–74 years age group compared with those aged 55–69 years. CONCLUSIONS This study of a large general risk population supports previous work that recent use of aspirin and ibuprofen is associated with a decreased risk of colorectal adenomas and demonstrates that this protective effect may be stronger in certain population subgroups and is also evident for aspirin and hyperplastic polyps.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Polyps in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Johnson

Hayes

Schoen

et al. 2010

American Journal of Gastroenterology

View full text Add to dashboard Cite

show abstract

“…Increased levels of COX-2 mRNA and proteins are found in premalignant lesions and malignant tissues of colitic cancer, making it an attractive therapeutic target (44). Chemoprevention of CRC is already possible with celecoxib, although it is still not the ultimate drug of choice, especially because of the cardiovascular risk associated with COX-2 inhibitors, by which agent targeted for prevention of colon cancer should exert inhibition of COX-2 but maintenance of PGDH, tumor suppressor gene related to COX-2 (45,46). Exogenous 8-OHdG was very efficient in either suppressing COX-2 expression or decreasing mucosal levels of PGE 2 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine

Ock

Kim²,

Hong³

et al. 2011

Cancer Prevention Research

View full text Add to dashboard Cite

Colitis-associated cancer (CAC) is one of clear examples of inflammation-carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-kB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSSinduced colitis as well as various inflammatory mediators such as TNF-a, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG-containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG-containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG-treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and b-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC. Cancer Prev Res; 4(9); 1507-21. Ó2011 AACR.

show abstract

“…The Aspirin Esomeprazole Chemoprevention Trial (AspECT; EudraCT number: 2004-003836-77) has been designed to test a high dose (80 mg) and a low dose (20 mg) of esomeprazole with either LDA (300 mg) or no aspirin. 32,33,67 The study is in the follow-up phase, with estimated study completion in 2019.…”

Section: Benefits Of Aspirin and Ppis In Preventing Be Colorectal Amentioning

confidence: 99%

Aspirin and Proton Pump Inhibitor Combination Therapy for Prevention of Cardiovascular Disease and Barrett's Esophagus

Peura

Wilcox

2014

Postgraduate Medicine

View full text Add to dashboard Cite

Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

show abstract

Cyclooxygenase-2 Inhibitors in Colorectal Cancer Prevention: Counterpoint

Cited by 36 publications

References 45 publications

Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Polyps in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Non-Steroidal Anti-Inflammatory Drug Use and Colorectal Polyps in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine

Aspirin and Proton Pump Inhibitor Combination Therapy for Prevention of Cardiovascular Disease and Barrett's Esophagus

Contact Info

Product

Resources

About