Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis

Neill, Annette S., Nagle, Christina M., Protani, Melinda M., Obermair, Andreas, Spurdle, Amanda B. and Webb, Penelope M. (2013) Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis. International Journal of Cancer, 132 5: 1146-1155. doi:10.1002/ijc.27717

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Author Neill, Annette S.
Nagle, Christina M.
Protani, Melinda M.
Obermair, Andreas
Spurdle, Amanda B.
Webb, Penelope M.
Title Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2013-03-01
Year available 2012
Sub-type Article (original research)
DOI 10.1002/ijc.27717
Open Access Status Not Open Access
Volume 132
Issue 5
Start page 1146
End page 1155
Total pages 10
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract Nonsteroidal anti-inflammatory drugs (NSAIDS) have received increasing attention as potential chemopreventive agents of skin cancer, but evidence is inconsistent. To investigate whether the use of aspirin and other NSAIDS reduces the risk of squamous cell carcinoma (SCC), we conducted a systematic review on the basis of published epidemiologic studies and calculated summary estimates for aspirin, nonaspirin NSAIDS, and any NSAIDS use. Summary estimates from nine studies (five case-control, three cohort, and one intervention) indicated significantly reduced risks of SCC among users of nonaspirin NSAIDS (relative risk (RR) 0.85, 95% confidence interval (CI) 0.78-0.94) and among users of any NSAIDS (RR 0.82, 95% CI 0.71-0.94) compared with nonusers with the effect seen particularly in those with previous actinic skin tumors. A reduced risk was also observed among aspirin users, although with borderline statistical significance (RR 0.88 95% CI 0.75-1.03). There was significant heterogeneity between studies regarding SCC risk estimates for aspirin use and any NSAIDS use. These findings suggest that NSAIDS collectively have the potential to prevent the development of cutaneous SCC.
Formatted abstract
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of a number of cancer types, however, previous studies of endometrial cancer have yielded inconclusive results. We analyzed data from the Australian National Endometrial Cancer Study (ANECS), a population-based case–control study (1,398 cases, 740 controls). We systematically reviewed all the evidence linking aspirin/NSAIDs use with endometrial cancer and conducted a meta-analysis. For ANECS, unconditional logistic regression was used to estimate odds ratios (OR) adjusting for potential confounders. For the systematic review, we searched Pubmed, Embase, Web of Science and conducted a review of citations from retrieved articles. The meta-analysis risk estimates were pooled using a random-effects model. In our case–control study, women who had ever used aspirin in the last 5 years had a significantly lower risk of endometrial cancer OR = 0.78 [95% confidence interval (CI): 0.63-0.97]. There was a significant inverse dose–response (p-trend <0.001) such that women who reported using ≥2 aspirin/week had almost half the risk OR = 0.54 (0.38–0.78). No significant associations were observed between use of half-aspirin/day, non-aspirin NSAIDs or paracetamol and endometrial cancer risk. The results were similar when examined by cancer subtype. Nine studies were included in the meta-analysis. The overall pooled risk estimate for any versus no use of aspirin was 0.87 (0.79–0.96) with no evidence of heterogeneity. The pooled risk estimate for obese women (BMI ≥ 30 kg/m2) was 0.72 (0.58–0.90) but there was no association for non-obese women. Overall these results suggest that aspirin may reduce the risk of endometrial cancer, particularly among obese women.
Keyword Endometrial cancer
Aspirin (acetylsalicylic acid)
Nonsteroidal anti-inflammatory drugs
Paracetamol (acetaminophen)
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 339435
Institutional Status UQ
Additional Notes Article first published online: 27 July 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Public Health Publications
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 32 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 34 times in Scopus Article | Citations
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Created: Wed, 14 Nov 2012, 23:14:27 EST by Matthew Lamb on behalf of School of Medicine