Skip to main content

Advertisement

SpringerLink
Log in

Analgesic use and the risk of primary adult brain tumor

  • CANCER
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case–control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Siegel R, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. doi:10.3322/caac.21332.

    Article  PubMed  Google Scholar 

  2. Kohler BA, Ward E, McCarthy BJ, et al. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst. 2011;103(9):714–36. doi:10.1093/jnci/djr077.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Stupp R, Hegi ME, Gilbert MR, Chakravarti A. Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol. 2007;25(26):4127–36. doi:10.1200/JCO.2007.11.8554.

    Article  CAS  PubMed  Google Scholar 

  4. Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro-oncology. 2012;14(Suppl 5):v1–49. doi:10.1093/neuonc/nos218.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Fang Z, Kulldorff M, Gregorio DI. Brain cancer mortality in the United States, 1986 to 1995: a geographic analysis. Neuro-oncology. 2004;6(3):179–87. doi:10.1215/S1152851703000450.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41(8):899–904. doi:10.1038/ng.407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wrensch M, Jenkins RB, Chang JS, et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41(8):905–8. doi:10.1038/ng.408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dobbins SE, Broderick P, Melin B, et al. Common variation at 10p12.31 near MLLT10 influences meningioma risk. Nat Genet. 2011;43(9):825–7. doi:10.1038/ng.879.

    Article  CAS  Google Scholar 

  9. Braganza MZ, Kitahara CM, de Gonzalez AB, Inskip PD, Johnson KJ, Rajaraman P. Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review. Neuro-oncology. 2012;14(11):1316–24. doi:10.1093/neuonc/nos208.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nature reviews. Clin Oncol. 2012;9(5):259–67. doi:10.1038/nrclinonc.2011.199.

    CAS  Google Scholar 

  11. Greenhough A, Smartt HJ, Moore AE, et al. The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis. 2009;30(3):377–86. doi:10.1093/carcin/bgp014.

    Article  CAS  PubMed  Google Scholar 

  12. Cha YI, DuBois RN. NSAIDs and cancer prevention: targets downstream of COX-2. Annu Rev Med. 2007;58:239–52. doi:10.1146/annurev.med.57.121304.131253.

    Article  CAS  PubMed  Google Scholar 

  13. Joki T, Heese O, Nikas DC, et al. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res. 2000;60(17):4926–31.

    CAS  PubMed  Google Scholar 

  14. Shono T, Tofilon PJ, Bruner JM, Owolabi O, Lang FF. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res. 2001;61(11):4375–81.

    CAS  PubMed  Google Scholar 

  15. Prayson RA, Castilla EA, Vogelbaum MA, Barnett GH. Cyclooxygenase-2 (COX-2) expression by immunohistochemistry in glioblastoma multiforme. Ann Diagn Pathol. 2002;6(3):148–53.

    Article  PubMed  Google Scholar 

  16. Castilla EA, Prayson RA, Kanner AA, et al. Cyclooxygenase-2 in oligodendroglial neoplasms. Cancer. 2003;98(7):1465–72. doi:10.1002/cncr.11632.

    Article  CAS  PubMed  Google Scholar 

  17. Perdiki M, Korkolopoulou P, Thymara I, et al. Cyclooxygenase-2 expression in astrocytomas. Relationship with microvascular parameters, angiogenic factors expression and survival. Mol Cell Biochem. 2007;295(1–2):75–83. doi:10.1007/s11010-006-9275-7.

    Article  CAS  PubMed  Google Scholar 

  18. Buccoliero AM, Caldarella A, Arganini L, et al. Cyclooxygenase-2 in oligodendroglioma: possible prognostic significance. Neuropathology. 2004;24(3):201–7.

    Article  PubMed  Google Scholar 

  19. Kokoglu E, Tuter Y, Sandikci KS, et al. Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors. Cancer Lett. 1998;132(1–2):17–21.

    Article  CAS  PubMed  Google Scholar 

  20. Loh JK, Hwang SL, Lieu AS, Huang TY, Howng SL. The alteration of prostaglandin E2 levels in patients with brain tumors before and after tumor removal. J Neurooncol. 2002;57(2):147–50.

    Article  PubMed  Google Scholar 

  21. Rolle CE, Sengupta S, Lesniak MS. Mechanisms of immune evasion by gliomas. Adv Exp Med Biol. 2012;746:53–76. doi:10.1007/978-1-4614-3146-6_5.

    Article  CAS  PubMed  Google Scholar 

  22. Xu K, Shu HK. EGFR activation results in enhanced cyclooxygenase-2 expression through p38 mitogen-activated protein kinase-dependent activation of the Sp1/Sp3 transcription factors in human gliomas. Cancer Res. 2007;67(13):6121–9. doi:10.1158/0008-5472.CAN-07-0141.

    Article  CAS  PubMed  Google Scholar 

  23. Wakimoto N, Wolf I, Yin D, et al. Nonsteroidal anti-inflammatory drugs suppress glioma via 15-hydroxyprostaglandin dehydrogenase. Cancer Res. 2008;68(17):6978–86. doi:10.1158/0008-5472.CAN-07-5675.

    Article  CAS  PubMed  Google Scholar 

  24. Sareddy GR, Geeviman K, Ramulu C, Babu PP. The nonsteroidal anti-inflammatory drug celecoxib suppresses the growth and induces apoptosis of human glioblastoma cells via the NF-kappaB pathway. J Neuro Oncol. 2012;106(1):99–109. doi:10.1007/s11060-011-0662-x.

  25. Kardosh A, Blumenthal M, Wang WJ, Chen TC, Schonthal AH. Differential effects of selective COX-2 inhibitors on cell cycle regulation and proliferation of glioblastoma cell lines. Cancer Biol Ther. 2004;3(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  26. Tai HH, Chi X, Tong M. Regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins Other Lipid Mediat. 2011;96(1–4):37–40. doi:10.1016/j.prostaglandins.2011.06.005.

    Article  CAS  PubMed  Google Scholar 

  27. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41. doi:10.1016/S0140-6736(10)62110-1.

    Article  CAS  PubMed  Google Scholar 

  28. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005;294(1):47–55. doi:10.1001/jama.294.1.47.

    Article  CAS  PubMed  Google Scholar 

  29. Sivak-Sears NR, Schwartzbaum JA, Miike R, Moghadassi M, Wrensch M. Case–control study of use of nonsteroidal antiinflammatory drugs and glioblastoma multiforme. Am J Epidemiol. 2004;159(12):1131–9. doi:10.1093/aje/kwh153.

    Article  PubMed  Google Scholar 

  30. Scheurer ME, El-Zein R, Thompson PA, et al. Long-term anti-inflammatory and antihistamine medication use and adult glioma risk. Cancer Epidemiol Biomark Prev. 2008;17(5):1277–81. doi:10.1158/1055-9965.EPI-07-2621.

    Article  CAS  Google Scholar 

  31. Scheurer ME, Amirian ES, Davlin SL, Rice T, Wrensch M, Bondy ML. Effects of antihistamine and anti-inflammatory medication use on risk of specific glioma histologies. Int J Cancer. 2011;129(9):2290–6. doi:10.1002/ijc.25883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ferris JS, McCoy L, Neugut AI, Wrensch M, Lai R. HMG, CoA reductase inhibitors, NSAIDs and risk of glioma. Int J Cancer. 2012;131(6):E1031–7. doi:10.1002/ijc.27536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ratnasinghe LD, Graubard BI, Kahle L, Tangrea JA, Taylor PR, Hawk E. Aspirin use and mortality from cancer in a prospective cohort study. Anticancer Res. 2004;24(5B):3177–84.

    PubMed  Google Scholar 

  34. Daugherty SE, Moore SC, Pfeiffer RM, et al. Nonsteroidal anti-inflammatory drugs and glioma in the NIH-AARP Diet and Health Study cohort. Cancer Prev Res. 2011;4(12):2027–34. doi:10.1158/1940-6207.CAPR-11-0274.

    Article  CAS  Google Scholar 

  35. Thun MJ, Namboodiri MM, Calle EE, Flanders WD, Heath CW Jr. Aspirin use and risk of fatal cancer. Cancer Res. 1993;53(6):1322–7.

    CAS  PubMed  Google Scholar 

  36. Gaist D, Garcia-Rodriguez LA, Sorensen HT, Hallas J, Friis S. Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma: a case–control study. Br J Cancer. 2013;108(5):1189–94. doi:10.1038/bjc.2013.87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bannon FJ, O’Rorke MA, Murray LJ, et al. Non-steroidal anti-inflammatory drug use and brain tumour risk: a case–control study within the Clinical Practice Research Datalink. CCC. 2013;. doi:10.1007/s10552-013-0279-9.

    PubMed  Google Scholar 

  38. Friis S, Sorensen HT, McLaughlin JK, Johnsen SP, Blot WJ, Olsen JH. A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin. Br J Cancer. 2003;88(5):684–8. doi:10.1038/sj.bjc.6600760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Anic GM, Madden MH, Sincich K, et al. Early life exposures and the risk of adult glioma. Eur J Epidemiol. 2013;28(9):753–8. doi:10.1007/s10654-013-9811-1.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Horwitz RI, Feinstein AR. The problem of “protopathic bias” in case–control studies. Am J Med. 1980;68(2):255–8.

    Article  CAS  PubMed  Google Scholar 

  41. Schwartzbaum J, Jonsson F, Ahlbom A, et al. Prior hospitalization for epilepsy, diabetes, and stroke and subsequent glioma and meningioma risk. Cancer Epidemiol Biomark Prev. 2005;14(3):643–50. doi:10.1158/1055-9965.EPI-04-0119.

    Article  Google Scholar 

  42. Culic V. Aspirin for preventing venous thromboembolism. N Engl J Med. 2013;368(8):772. doi:10.1056/NEJMc1215492#SA1.

    Article  PubMed  Google Scholar 

  43. Gasic GJ, Gasic TB, Stewart CC. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci USA. 1968;61(1):46–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gasic GJ, Gasic TB, Murphy S. Anti-metastatic effect of aspirin. Lancet. 1972;2(7783):932–3.

    Article  CAS  PubMed  Google Scholar 

  45. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006;55(1):115–22. doi:10.1136/gut.2004.047100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Doherty GA, Murray FE. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age? Expert Opin Ther Targets. 2009;13(2):209–18. doi:10.1517/14728220802653631.

    Article  CAS  PubMed  Google Scholar 

  47. Hung WC. Anti-metastatic action of non-steroidal anti-inflammatory drugs. Kaohsiung J Med Sci. 2008;24(8):392–7. doi:10.1016/S1607-551X(08)70162-1.

    Article  CAS  PubMed  Google Scholar 

  48. Ruschoff J, Wallinger S, Dietmaier W, et al. Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Proc Natl Acad Sci USA. 1998;95(19):11301–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McIlhatton MA, Tyler J, Burkholder S, et al. Nitric oxide-donating aspirin derivatives suppress microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells. Cancer Res. 2007;67(22):10966–75. doi:10.1158/0008-5472.CAN-07-2562.

    Article  CAS  PubMed  Google Scholar 

  50. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G. Aspirin, salicylates, and cancer. Lancet. 2009;373(9671):1301–9. doi:10.1016/S0140-6736(09)60243-9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge the study participants and their families. We further wish to thank the clinicians and research staffs at participating medical centers for their contributions. In addition, we acknowledge Harold Colbassani, MD; Dean Gobo, MD; and Christopher Mickler, DO at Morton Plant Mease Healthcare and Baycare Health System in Clearwater, FL for their efforts recruiting subjects to the study. The project was supported by the National Institutes of Health (R01CA116174 and R25 CA147832), and institutional funding provided by the Moffitt Cancer Center (Tampa, FL) and the Vanderbilt-Ingram and Comprehensive Cancer Center (Nashville, TN).

Author information

Authors and Affiliations

  1. Division of Population Sciences, Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, MRC-CANCONT, Tampa, FL, 33612-9416, USA

    Kathleen M. Egan, Zachary J. Thompson, Carrie M. Rozmeski & Gabriella A. Anic

  2. Neuro-Oncology Program, University of Alabama at Birmingham, FOT 1020, 510 20th St. South, Birmingham, AL, 35294, USA

    Louis B. Nabors

  3. Department of Neurosurgery, Emory University School of Medicine, 1365-B Clifton Rd., NE, Ste. 2200, Atlanta, GA, 30322, USA

    Jeffrey J. Olson

  4. Department of Hematology-Oncology, Norton Cancer Institute, 315 E. Broadway, Louisville, KY, 40202, USA

    Renato V. LaRocca

  5. Neuro-Oncology Program, Lynn Cancer Institute and the Boca Raton Regional Hospital, 701 NW 13th Street, Boca Raton, FL, 33486, USA

    Sajeel A. Chowdhary

  6. Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Peter A. Forsyth

  7. Department of Neurological Surgery, Vanderbilt University Medical Center, 691 Preston Building, Nashville, TN, 37232, USA

    Reid C. Thompson

Authors
  1. Kathleen M. Egan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Louis B. Nabors
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zachary J. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carrie M. Rozmeski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gabriella A. Anic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey J. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renato V. LaRocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sajeel A. Chowdhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peter A. Forsyth
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Reid C. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathleen M. Egan.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Egan, K.M., Nabors, L.B., Thompson, Z.J. et al. Analgesic use and the risk of primary adult brain tumor. Eur J Epidemiol 31, 917–925 (2016). https://doi.org/10.1007/s10654-016-0129-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-016-0129-7

Keywords

Search

Navigation