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Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk

Abstract

Background

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs).

Methods

Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden.

Results

The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85–0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30–0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85–0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53–0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96–1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29–0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88–0.95).

Conclusions

This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.

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References

  1. Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc Natl Acad Sci USA. 1995;92:5258–65.

    Article  CAS  Google Scholar 

  2. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  CAS  Google Scholar 

  3. Stark T, Livas L, Kyprianou N. Inflammation in prostate cancer progression and therapeutic targeting. Transl Androl Urol. 2015;4:455–63.

    PubMed  PubMed Central  Google Scholar 

  4. Schatteman PHF, Hoekx L, Wyndaele JJ, Jeuris W, Van Marck E. Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis - Correlation with total serum PSA and PSA density. Eur Urol. 2000;37:404–12.

    Article  CAS  Google Scholar 

  5. Gurel B, Lucia MS, Thompson IM, Goodman PJ, Tangen CM, Kristal AR, et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidem Biomar. 2014;23:847–56.

    Article  Google Scholar 

  6. Fujita K, Hosomi M, Tanigawa G, Okumi M, Fushimi H, Yamaguchi S. Prostatic inflammation detected in initial biopsy specimens and urinary pyuria are predictors of negative repeat prostate biopsy. J Urol. 2011;185:1722–7.

    Article  Google Scholar 

  7. Knights KM, Mangoni AA, Miners JO. Defining the COX inhibitor selectivity of NSAIDs: implications for understanding toxicity. Expert Rev Clin Pharmacol. 2010;3:769–76.

    Article  CAS  Google Scholar 

  8. Kargman S, Charleson S, Cartwright M, Frank J, Riendeau D, Mancini J, et al. Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts. Gastroenterology. 1996;111:445–54.

    Article  CAS  Google Scholar 

  9. Harris RC, Mckanna JA, Akai Y, Jacobson HR, Dubois RN, Breyer MD. Cyclooxygenase-2 is associated with the macula densa of rat-kidney and increases with salt restriction. J Clin Invest. 1994;94:2504–10.

    Article  CAS  Google Scholar 

  10. Hirst JJ, Teixeira FJ, Zakar T, Olson DM. Prostaglandin endoperoxide-h synthase-1 and synthase-2 messenger-ribonucleic-acid levels in human amnion with spontaneous labor onset. J Clin Endocr Metab. 1995;80:517–23.

    CAS  PubMed  Google Scholar 

  11. Hamasaki Y, Kitzler J, Hardman R, Nettesheim P, Eling TE. Phorbol ester and epidermal growth-factor enhance the expression of 2 inducible prostaglandin-h synthase genes in rat tracheal epithelial-cells. Arch Biochem Biophys. 1993;304:226–34.

    Article  CAS  Google Scholar 

  12. De Marzo AM, Platz EA, Sutcliffe S, Xu JF, Gronberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256–69.

    Article  Google Scholar 

  13. Wennogle LP, Liang HB, Quintavalla JC, Bowen BR, Wasvary J, Miller DB, et al. Comparison of recombinant cyclooxygenase-2 to native isoforms - aspirin labeling of the active-site. FEBS Lett. 1995;371:315–20.

    Article  CAS  Google Scholar 

  14. Patrignani P, Patrono C. Aspirin and cancer. J Am Coll Cardiol. 2016;68:967–76.

    Article  CAS  Google Scholar 

  15. Liu Y, Chen J-Q, Xie L, Wang J, Li T, He Y, et al. Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis. BMC Med. 2014;12:55–69.

    Article  CAS  Google Scholar 

  16. Vidal AC, Howard LE, Moreira DM, Castro-Santamaria R, Andriole GL, Freedland SJ. Aspirin, NSAIDs, and risk of prostate cancer: results from the REDUCE study. Clin Cancer Res. 2015;21:756–62.

    Article  CAS  Google Scholar 

  17. Bonovas S, Filioussi K, Sitaras NM. Statin use and the risk of prostate cancer: a metaanalysis of 6 randomized clinical trials and 13 observational studies. Int J Cancer. 2008;123:899–904.

    Article  CAS  Google Scholar 

  18. Zhang Y, Zang T. Association between statin usage and prostate cancer prevention: a refined meta-analysis based on literature from the years 2005-2010. Urol Int. 2013;90:259–62.

    Article  CAS  Google Scholar 

  19. Tan P, Zhang C, Wei SY, Tang Z, Gao L, Yang L, et al. Effect of statins type on incident prostate cancer risk: a meta-analysis and systematic review. Asian J Androl. 2016; Epub ahead of print (cited 2017 Jul 17). http://www.ajandrology.com/preprintarticle.asp?id=190327.

  20. Bansal D, Undela K, D’Cruz S, Schifano F, Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE.2012;7:e46691

    Article  CAS  Google Scholar 

  21. Mattsson B, Wallgren A. Completeness of the Swedish Cancer Register - Non-Notified Cancer Cases Recorded on Death Certificates in 1978. Acta Radiol Oncol. 1984;23:305–13.

    Article  CAS  Google Scholar 

  22. FASS (Farmacevtiska specialiteter i Sverige) [Internet]. 2015. Available from: www.fass.se.

  23. Kyriazi V, Theodoulou E. Assessing the risk and prognosis of thrombotic complications in cancer patients. Arch Pathol Lab Med. 2013;137:1286–95.

    Article  Google Scholar 

  24. Allott EH, Howard LE, Vidal AC, Moreira DM, Castro-Santamaria R, Andriole GL, et al. Statin use, serum lipids, and prostate inflammation in men with a negative prostate biopsy: results from the REDUCE trial. Cancer Prev Res. 2017;10:319–25.

    Article  CAS  Google Scholar 

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Acknowledgments

SFO epidemiology (Karolinska Institutet).

Authors’ contributions

Literature search: Y.M.+N.B.; design of the study: Y.M.+N.B.; data collection and preparation for analyzes: N.B.; data analysis: Y.M.+N.B.; data interpretation: Y.M.+N.B.; writing of first draft: Y.M., revised and approved by all authors.

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Correspondence to Yuanjun Ma.

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Ma, Y., Brusselaers, N. Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk. Prostate Cancer Prostatic Dis 21, 147–152 (2018). https://doi.org/10.1038/s41391-017-0021-x

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