Skip to main content
SpringerLink
Log in

Acetylsalicylsäure und Prävention kolorektaler Karzinome

Aspirin and prevention of colorectal carcinomas

  • Arzneimitteltherapie
  • Published:
Der Internist Aims and scope Submit manuscript

Zusammenfassung

Acetylsalicylsäure (ASS) hemmt nach dem übereinstimmenden Ergebnis epidemiologischer, aber auch einiger randomisierter Studien die Entstehung und Progression kolorektaler Neoplasien (Adenome, Karzinome). Viele Fragen sind jedoch noch offen, insbesondere zum Nutzen-Risiko-Verhältnis (Blutungen!), aber ebenso zur Dosis und Behandlungsdauer bei der vermutlich erforderlichen Langzeitmedikation. Auch ist bisher weder ein allgemein akzeptierter Wirkungsmechanismus von ASS noch eine klar definierte molekulare Zielstruktur bekannt, obwohl ein Zusammenhang mit der Senkung tumorassoziiert erhöhter Prostaglandin-E2-Spiegel in der Darmmukosa wahrscheinlich ist. Die tägliche Einnahme von ASS in Antiplättchendosen von 100 mg/Tag scheint bei darauf ansprechenden Personen ausreichend wirksam zu sein. Sollten diese interessanten Befunde einschließlich der Wirksamkeit von niedrig dosierter ASS in derzeit laufenden prospektiven, randomisierten Studien bestätigt werden, könnte dies eine Erweiterung der prophylaktischen ASS-Anwendung bedeuten. Darüber hinaus würde es eine Hemmung der Cyclooxygenase-1-vermittelten Prostaglandin- und Thromboxansynthese als gemeinsamen primären Wirkort für eine kardiokoronare und antineoplastische Chemoprävention wahrscheinlich machen. Unter dem prophylaktischen Aspekt sollte man darüber allerdings nicht die unstrittige Bedeutung eines gesunden Lebensstils einschließlich gesunder Ernährung vergessen.

Abstract

Observational and some randomized clinical trials suggest that aspirin protects from occurrence and progression of colorectal neoplasias (adenomas, carcinomas). However, there are still open questions, regarding the benefit/risk ratio (bleedings) as well as dosage and duration of treatment during the probably long-term medication, before stringent recommendations regarding clinical use of aspirin can be made. Specifically, there is currently no generally accepted mode of action or molecular target of aspirin, though a relationship to tumor-associated enhanced PGE2 levels in the affected mucosa is likely. Regular daily intake of aspirin in antiplatelet doses of 100 mg appears to be sufficient in responding persons. If this is confirmed in prospective randomized trials that are currently underway, this might add to the prophylactic use of aspirin and would suggest a pharmacological relationship to inhibition of COX-1 mediated prostaglandin/thromboxane biosynthesis as a common primary target for both cardiocoronary and antineoplastic prophylaxis. Prophylactic aspirin use might then add to an undoubtedly important healthy lifestyle including appropriate diet.

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

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Bambace NM, Holmes CE (2010) The platelet contribution to cancer progression. J Thromb Haemost 9:237–249

    Google Scholar 

  2. Baron J (2012) Aspirin and cancer: trials and observational studies. J Natl Cancer Inst 104:1199–1200

    Google Scholar 

  3. Bastiannet E, Sampieri K, Dekkers OM et al (2012) Use of aspirin post diagnosis improves survival for colon cancer patients. Br J Cancer 106:1564–1570

    Article  Google Scholar 

  4. Burn J, Gerdes A-M, Macray F et al (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378:2081–2087

    Article  PubMed  Google Scholar 

  5. Castellone M, Teramoto H, Gutkind S (2006) Cyclooxygenase-2 and colorectal cancer chemoprevention: the β-catenin-connection. Cancer Res 66:11085–11088

    Article  PubMed  CAS  Google Scholar 

  6. Chan AT, Ogino S, Fuchs CS (2009) Aspirin use and survival after diagnosis of colorectal cancer. JAMA 302:649–658

    Article  PubMed  CAS  Google Scholar 

  7. Chan A, Arber N, Burn J et al (2011) Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev Res 5:164–178

    Article  Google Scholar 

  8. Chulada PC, Thompson MB, Mahler JF et al (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res 60:4705–4708

    PubMed  CAS  Google Scholar 

  9. Cole BF, Logan RF, Halabi S et al (2009) Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 101:256–266

    Google Scholar 

  10. Cuzick J, Otto F, Baron JA et al (2009) Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 10:501–507

    Article  PubMed  CAS  Google Scholar 

  11. Din FVN, Theodoratu E, Farrington SM et al (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59:1670–1679

    Article  PubMed  CAS  Google Scholar 

  12. Eisinger AL, Prescott SM, Jones DA et al (2007) The role of cyclooxygenase-2 and prostaglandins in colon cancer. Prostaglandins Other Lipid Mediat 82:147–154

    Article  PubMed  CAS  Google Scholar 

  13. Hohlfeld T, Saxena A, Schrör K (2013) High on treatment platelet reactivity against aspirin by non-steroidal anti-inflammatory drugs – pharmacological mechanisms and clinical relevance. Thromb Haemost (im Druck)

  14. Jacobs EJ, Newton CC, Gapstur SM et al (2012) Daily aspirin use and cancer mortality in a large US cohort. J Natl Cancer Inst 104:1208–1217

    Google Scholar 

  15. Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 48:4399–4404

    PubMed  CAS  Google Scholar 

  16. Liang J, Nagahashi M, Kim E et al (2013) Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 23:107–120

    Article  PubMed  CAS  Google Scholar 

  17. Liao X, Lochhead P, Nishihara R et al (2012) Aspirin use, tumor PIK3CA mutation, and colorectal survival. N Engl J Med 367:1596–1606

    Google Scholar 

  18. Rothwell PM, Fowkes FG, Belch JF et al (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet 377:31–43

    Article  PubMed  CAS  Google Scholar 

  19. Rothwell PM, Price JF, Fowkes GR (2012) Short-term effects of daily aspirin on cancer incidence, mortality and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379:1602–1612

    Article  PubMed  CAS  Google Scholar 

  20. Rothwell PM, Wilson M, Price JF et al (2012) Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomized controlled trials. Lancet 379:1591–1601

    Article  PubMed  CAS  Google Scholar 

  21. Ruffin MT, Krishnan K, Rock CL et al (1997) Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose. J Natl Cancer Inst 89:1152–1160

    Google Scholar 

  22. Schneider R, Schneider C, Kloor M et al (2012) Lynch syndrome: clinical, pathological and genetic insights. Langenbecks Arch Surg 397:513–525

    Article  PubMed  Google Scholar 

  23. Schrör K (2011) Pharmacology and cellular/molecular mechanism of action of aspirin and non-aspirin NSAIDs in colorectal cancer. Best Pract Res Clin Gastroenterol 25:473–484

    Article  PubMed  Google Scholar 

  24. Schrör K (2011) Acetylsalicylsäure. Dr. Schrör, Frechen

  25. Smartt HJM, Greenhough A, Ordonez-Moran P et al (2012) β-Catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells. Gut 61:1306–1314

    Article  PubMed  CAS  Google Scholar 

  26. Ulrych T, Böhm A, Polzin A et al (2011) Release of sphingosine-1-phosphate from human platelets is dependent on thromboxane formation. J Thromb Haemost 9:790–798

    Google Scholar 

  27. Yan M, Myung S-J, Fink SP et al (2009) 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colonic tumors. Proc Natl Acad Sci U S A 106:9409–9413

    Article  Google Scholar 

  28. Yu HG, Huang JA, Yang YN et al (2002) The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells. Eur J Clin Invest 32:838–846

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist für sich und seinen Koautor auf folgende Beziehungen hin: K. Schrör ist Mitglied eines Advisory Boards der Fa. Bayer und nimmt eine honorierte Vortragstätigkeit für diese Firma wahr. Ein experimentelles Forschungsprojekt von B.H. Rauch zum Mechanismus der antineoplastischen ASS-Wirkung wird von der Fa. Bayer unterstützt.

Author information

Authors and Affiliations

  1. Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Moorenstr. 5, 40225, Düsseldorf, Deutschland

    K. Schrör

  2. Institut für Pharmakologie, Abteilung Allgemeine Pharmakologie, Ernst-Moritz-Arndt-Universität, Greifswald, Deutschland

    B.H. Rauch

Authors
  1. K. Schrör
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B.H. Rauch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Schrör.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schrör, K., Rauch, B. Acetylsalicylsäure und Prävention kolorektaler Karzinome. Internist 54, 884–891 (2013). https://doi.org/10.1007/s00108-013-3311-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00108-013-3311-y

Schlüsselwörter

Keywords

Search

Navigation