Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis

Abnet, Christian C.; Freedman, Neal D.; Kamangar, Farin; Leitzmann, Michael F.; Hollenbeck, Albert R.; Schatzkin, Arthur

doi:10.1038/sj.bjc.6604880

Cited by 165 publications

(173 citation statements)

References 42 publications

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“…(Jemal et al, 2007) It is therefore important to identify aetiological and protective factors for this disease to improve primary prevention. Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been reported to reduce the risk of several cancers and some pre-malignant lesions, with risk reductions ranging from 20% to 50% for certain cancer sites (Garcia- Rodriguez and HuertaAlvarez, 2001;Khuder and Mutgi, 2001;Gonzalez-Perez et al, 2003;Abnet et al, 2009;Cole et al, 2009).…”

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confidence: 99%

Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case–control study

et al. 2010

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BACKGROUND: Non-steroidal anti-inflammatory drug (NSAID) use has been linked with pancreatic cancer risk; however, findings from epidemiological studies are inconsistent. METHODS: A nested case -control study was conducted within the UK General Practice Research Database. Cases (n ¼ 1141) had a diagnosis of primary cancer of the exocrine pancreas between January 1995 and June 2006. Controls (n ¼ 7954) were matched with each case on general practice site, sex and year of birth. Conditional logistic regression analyses were used to generate odds ratios (OR) and 95% confidence intervals (CI) associated with NSAID use compared with non-use. RESULTS: Any use of NSAID in the 5 years before the index date or since entry into the database (excluding the year before diagnosis) was not associated with risk of pancreatic cancer; OR 0.96 (95% CI, 0.84 -1.10) and 1.03 (95% CI 0.89 -1.19), respectively. Exposure to NSAIDs for 4 773 days, in the 5 years pre-diagnosis, was associated with a reduced risk of pancreatic cancer OR 0.78 (95%CI 0.62 -0.97). There was evidence of reduced pancreatic cancer risk with long-term use (5 years or more) of lower doses of NSAIDs OR 0.70 (95% CI 0.49 -0.99). CONCLUSION: Long-term exposure to NSAIDs may be associated with a reduction in risk of pancreatic cancer.

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confidence: 99%

Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case–control study

et al. 2010

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“…Previous case-control and epidemiologic cohort studies have demonstrated that the orderly use of non-steroidal anti-inflammatory drugs decreased digestive tract malignancy mortalities, including colorectal and gastric adenocarcinoma (14,15). Consequently, the COX-2 enzyme is considered a potential therapeutic marker for the prevention and treatment of cancer.…”

Section: Discussionmentioning

confidence: 99%

Relationship between HER-2, COX-2, p53 and clinicopathologic features in gastric adenocarcinoma. Do these biomarkers have any prognostic significance?

Uğraş

Özgün²,

Ocakoğlu³

et al. 2015

Turk J Gastroenterol

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Background/Aims: The aim of this study was to examine the expression of HER-2, p53 and COX-2 in gastric adenocarcinoma and to investigate whether these markers were useful in predicting the clinicopathologic features. Materials and Methods: Primary gastric adenocarcinoma specimens were obtained from 56 patients who underwent total/subtotal gastrectomy with extended lymphadenectomy between December 2011 -December 2012. We investigated the association between the expression of these markers and clinicopathologic factors by immunohistochemistry. Results: COX-2 positive cases were detected in 28 (50%) of the 56 patients and COX-2 expression was significantly correlated with presence of perineural invasion (p=0,032). 37 cases (66.1%) were defined positive for p53. The expression of p53 was significantly correlated with increasing age (p=0,003), but there was no correlation with other clinicopathological variables. Among the 56 primary gastric cancers, 9 (16.1%) cases showed intermediate (2+) positive expression and 7 (12.5%) cases showed (3+) positive expression for HER-2. No significant correlations were determined between HER-2 and the other variables. Conclusion: Although, this study failed to show any relationship between HER-2 and clinicopathological factors, but our results demondtrated that COX-2 expression might serve as a powerful indicator for estimating perineural invasion, which is an independent worse prognostic factor for survival in gastric adenocarcinoma. Additionally, detecting the expression of p53 can assist with the treatment options for elderly patients with gastric adenocarcinoma. A better understanding of HER-2, COX-2 and p53 expression in gastric adenocarcinoma may improve the staging strategies and influence new treatment modalities.

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“…Thus, it cannot differentiate whether any beneficial effect of NSAID use is produced before or after BE appearance. In 2009, a questionnaire based study that included approximately 300000 members of the American Association of Retired Persons found no significant association between EAC and the use of aspirin or non-aspirin NSAIDs [36] . Since 2003, several observational studies comparing BE and EAC patients have been published (Table 1).…”

Section: Nsaids and Eac Chemopreventionmentioning

confidence: 99%

“…Nevertheless, the attributable risk is small (12 per 100000 person-years) and no change in cognitive function was found in randomized trials of statins in elderly patients [130] . Because BE patients are usually old with various multi-systemic comorbidities [36] , increased toxicity is expected [133] with statin use. No study today has specifically addressed statin toxicity in BE patients.…”

Section: Side Effects Of Statin Chemopreventionmentioning

confidence: 99%

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus

Tsibouris

Vlachou

Isaacs

2014

WJGPT

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The incidence of esophageal adenocarcinoma, a poor prognosis neoplasia, has risen dramatically in recent decades. Barrett's esophagus represents the best-known risk factor for esophageal adenocarcinoma development. Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation, increase cell apoptosis and regulate the expression of growth and angiogenic factors. Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades. At present, epidemiological studies are small and underpowered. Their data could not justify either medication as a chemo-preventive agent. Population based studies have shown a 43% reduction of the odds of developing an esophageal adenocarcinoma, leaving out or stating a 25% reduction in patients consuming non-aspirin nonsteroidal antiinflammatory drugs and a 50% reduction in those patients consuming aspirin. They have also stated a 19% reduction of esophageal cancer incidence when statins have been used. Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce the adenocarcinoma incidence in patients with Barrett's esophagus by 41%, while statins could reduce the risk by 43%. The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins (a 74% decrease). Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses. Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity, while statins are rather safe drugs. In conclusion, both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies. In the meanwhile, their use is justified only in patients with cardiovascular disease.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Esophageal adenocarcinoma; Barrett's esophagus; Non-steroidal anti-inflammatory drugs; Aspirin; Statins; Cancer chemoprevention Core tip: Esophageal adenocarcinoma remains a major burden upon health. Experimental studies have suggested that non-steroidal anti-inflammatory drugs and statins may have useful actions against esophageal cancer cells. This review of observational studies shows that non-steroidal anti-inflammatory drugs reduced adenocarcinoma incidence in patients with Barrett' s esophagus by 41%, while statins reduced the risk by 43%. The cancer preventive effect is enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins (a 74% decrease). Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity, while statins are rather safe drugs. Their combination offers promise for chemoprevention and further interventional studies are warranted.Tsibouris P, Vlachou E, Isaacs PET. Role of chemoprophylaxis REVIEWOnline Submissions: http://www.wjgnet.com/esps/

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Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis

Cited by 165 publications

References 42 publications

Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case–control study

Non-steroidal anti-inflammatory drugs and pancreatic cancer risk: a nested case–control study

Relationship between HER-2, COX-2, p53 and clinicopathologic features in gastric adenocarcinoma. Do these biomarkers have any prognostic significance?

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus

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