COX‐2 expression in sporadic colorectal adenomatous polyps is linked to adenoma characteristics

McLean, Mairi H; Murray, Graeme I.; Fyfe, Nicky; Hold, Georgina L.; Mowat, N. A. G.; El-Omar, Emad

doi:10.1111/j.1365-2559.2008.03038.x

Cited by 26 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings of a lack of association of dietary marinederived n23 PUFAs on hyperplastic, as opposed to adenomatous, polyp risk would be expected if the beneficial effects of n23 PUFAs are mediated through a reduction in prostaglandin E 2 . The overexpression of cyclooxygenase-2 has been well documented in adenomatous polyps but has been much less commonly described in hyperplastic polyps, which suggests that prostaglandin E 2 may not play as important a role in hyperplastic polyp development (52)(53)(54).…”

Section: Discussionmentioning

confidence: 98%

Dietary intake of PUFAs and colorectal polyp risk

Murff¹,

Shrubsole²,

Cai³

et al. 2012

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Dietary intake of PUFAs and colorectal polyp risk

Murff¹,

Shrubsole²,

Cai³

et al. 2012

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

show abstract

“…In models of allergic inflammation and colitis, PGE 2 is well known to have a protective role in limiting inflammation [61–65]. This is unlike initiated colon tissue where highly up-regulated COX-2 is known to have tumor-promoting effects [2, 3, 66]. This calls into question whether prevention in normal risk individuals who do not have any defined pathological changes in the colon would benefit from COX-1 or COX-2 inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of cyclooxygenase-2 (COX-2) and increased PGE 2 synthesis are hallmarks of colon cancer progression [1, 3–5]. Relatively less is known about the role of other arachidonic acid (AA) metabolites in colon cancer, but they do play a role in the inflammatory response and in carcinogenesis [6–8].…”

Section: Introductionmentioning

confidence: 99%

Effect of cyclooxygenase genotype and dietary fish oil on colonic eicosanoids in mice

Neilson

Djurić

Ren

et al. 2012

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Dietary ω3 fatty acids can modulate substrate availability for cyclooxygenases and lipoxygenases, thus modulating downstream eicosanoid formation. This could be an alternative approach to using NSAIDs and other COX inhibitors for limiting PGE2 synthesis in colon cancer prevention. The aims of this study were to evaluate to what extent cyclooxygenase- and lipoxygenase-derived products could be modulated by dietary fish oil in normal colonic mucosa, and to evaluate the role of COX-1 and COX-2 in formation of these products. Mice (wild-type, COX-1 null, or COX-2 null) were fed a diet supplying a broad mixture of fatty acids present in European/American diets, supplemented with either olive oil (oleate control diet) or menhaden (fish) oil ad libitum for 9–11 wk. Colonic eicosanoid levels were measured by LC-MS/MS, and proliferation was assessed by Ki67 immunohistochemistry. Dietary alteration of colonic arachidonic acid: eicosapentaenoic ratios resulted in large shifts in formation of cyclooxygenase and lipoxygenase metabolites. COX-1 knockout virtually abolished PGE2 formation but interestingly 12-HETE and 15-HETE formation was increased. The large changes in eicosanoid profiles were accompanied by relatively small changes in colonic crypt proliferation, but such changes in eicosanoid formation might have greater biological impact upon carcinogen challenge. These results indicate that in normal colon, inhibition of COX-2 would have little effect on reducing PGE2 levels.

show abstract

“…One possible mechanism for this difference in NSAID effects is likely related to the differential overexpression of COX-2 seen in adenomatous polyps as opposed to hyperplastic polyps. Although overexpression of COX-2 has been described in hyperplastic polyp specimens,(31) the strength of COX-2 overexpression is less in hyperplastic polyps compared to adenomatous polyps. (32, 33) Kawasaki et al found that 28% of non-serrated adenomas had strong overexpression of COX-2 compared to only 4.2% of hyperplastic polyps.…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal Anti-inflammatory Drug Use and Risk of Adenomatous and Hyperplastic Polyps

Murff

Shrubsole

Chen

et al. 2011

Cancer Prevention Research

View full text Add to dashboard Cite

Adenomatous polyps are known precursor lesions for colorectal cancer and some hyperplastic polyps also have malignant potential. The use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDS) is associated with a reduced risk of adenomatous polyps; however, less evidence exists regarding NSAID use and hyperplastic polyp risk. We conducted a colonoscopy-based case-control study including 2028 polyp cases (1,529 adenomatous and 499 hyperplastic) and 3,431 polyp-free controls. Multivariate logistic regression models were constructed to derived adjusted odds ratios (OR) and 95% confidence intervals (CI) as the measure of the association between NSAID use and polyp risk. Use of baby aspirin, regular aspirin, and non-aspirin NSAIDs, were associated with a reduced risk of adenomatous polyps (OR = 0.79; 95% CI 0.66–0.93, OR = 0.73; 0.58–0.90, and OR = 0.67; 0.53–0.86, respectively). Baby aspirin was also associated with a reduced risk of hyperplastic polyps (OR = 0.74; 0.56–0.97). Although a dose response was seen with adenoma risk and regular use of any NSAIDs (less than 7 doses per week, 7 doses per week, and greater than 7 doses per week), a dose response was not seen with hyperplastic polyps. We found no evidence of interaction between NSAID dose and duration and polyp risk. The use of any NSAID regardless of type was associated with a reduced risk of adenomatous polyps however regular aspirin and COX-2 inhibitors use was not associated with hyperplastic polyp risk.

show abstract

COX‐2 expression in sporadic colorectal adenomatous polyps is linked to adenoma characteristics

Abstract: This study associates COX-2 epithelial expression with a number of adenoma characteristics that convey an increased risk of malignant transformation. This is in keeping with a positive role for COX-2 in early colorectal carcinogenesis.

Cited by 26 publications

References 31 publications

Dietary intake of PUFAs and colorectal polyp risk

Dietary intake of PUFAs and colorectal polyp risk

Effect of cyclooxygenase genotype and dietary fish oil on colonic eicosanoids in mice

Nonsteroidal Anti-inflammatory Drug Use and Risk of Adenomatous and Hyperplastic Polyps

Contact Info

Product

Resources

About