Acetylsalicylsäure - ein geeignetes Mittel zur Krebsprävention?

Acetylsalicylsäure (ASS, Aspirin^® u. a.) ist ein Vertreter der NSAID („nonsteroidal antiinflammatory drugs“). (Die gelegentlich anzutreffende Unterscheidung zwischen ASS und NSAID ist irreführend. Der Begriff NSAID bezeichnet in Abgrenzung zu Opioid-Analgetika und Glucocorticoid-Antiphlogistika eine Gruppe von nichtsteroidalen Substanzen mit zumeist sauren Eigenschaften, die durch einen gemeinsamen Wirkmechanismus (Hemmung der Prostaglandinsynthese) und klinisch durch analgetische, antipyretische und antiphlogistische Wirkungen charakterisiert sind. Somit ist ASS ein prototypisches NSAID.)

Neben den bekannten antiinflammatorischen, analgetischen und antipyretischen Effekten besitzt ASS eine ebenfalls gut untersuchte thrombozytenaggregationshemmende Wirkung, die klinisch zur Prävention thrombotischer vaskulärer Ereignisse, insbesondere des Myokardinfarktes, genutzt wird [1] [2]. Seit den 1980er Jahren gibt es zunehmend Hinweise auf eine protektive Wirkung von ASS in der Prävention maligner Tumorerkrankungen. Die Ergebnisse jüngster epidemiologischer [3] [4] und klinischer Studien [5] [6] haben eine intensive Diskussion zum Nutzen von ASS in der Krebsprävention angestoßen.

Literatur

• 1 Anonymous . Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  BMJ. 2002;  324 71-86
• 2 Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the US Preventive Services Task Force.  Ann Intern Med. 2002;  136 161-172
• 3 Garcia-Rodriguez L A, Huerta-Alvarez C. Reduced risk of colorectal cancer amonglong-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs.  Epidemiology. 2001;  12 88-93
• 4 Bosetti C, Talamini R, Franceschi S, Negri E, Garavello W, La Vecchia C. Aspirin use and cancers of the upper aerodigestive tract.  Br J Cancer. 2003;  88 672-674
• 5 Baron J A, Cole B F, Sandler R S, Haile R W, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers R W, Rothstein R, Burke C A, Snover D C, Church T R, Allen J I, Beach M, Beck G J, Bond J H, Byers T, Greenberg E R, Mandel J S, Marcon N, Mott L A, Pearson L, Saibil F, van Stolk R U. A randomized trial of aspirin to prevent colorectal adenomas.  N Engl J Med. 2003;  348 891-899
• 6 Sandler R S, Halabi S, Baron J A, Budinger S, Paskett E, Keresztes R, Petrelli N, Pipas J M, Karp D D, Loprinzi C L, Steinbach G, Schilsky R. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.  N Engl J Med. 2003;  348 883-890
• 7 Vane J R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirinlike drugs.  Nat New Bio. 1971;  231 232-235
• 8 Thun M J, Henley S J, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues.  J Natl Cancer Inst. 2002;  94 252-266
• 9 Chan T A. Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention.  Lancet Oncol. 2002;  3 166-174
• 10 Eberhart C E, Coffey R J, Radhika A, Giardiello F M, Ferrenbach S, DuBois R N. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas.  Gastroenterology. 1994;  107 1183-1188
• 11 Ermert L, Dierkes C, Ermert M. Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors.  Clin Cancer Res. 2003;  9 1604-1610
• 12 Anderson W F, Umar A, Viner J L, Hawk E T. The role of cyclooxygenase inhibitors in cancer prevention.  Curr Pharm Des. 2002;  8 1035-1062
• 13 Sheehan K M, Sheahan K, O’Donoghue D P, MacSweeney F, Conroy R M, Fitzgerald D J, Murray F E. The relationship between cyclooxygenase-2 expression and colorectal cancer.  Jama. 1999;  282 1254-1257
• 14 Steinbach G, Lynch P M, Phillips R K, Wallace M H, Hawk E, Gordon G B, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su L K, Levin B. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.  N Engl J Med. 2000;  342 1946-1952
• 15 Sheng H, Shao J, Washington M K, DuBois R N. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells.  J Biol Chem. 2001;  276 18075-18081
• 16 Gupta R A, Tan J, Krause W F, Geraci M W, Willson T M, Dey S K, DuBois R N. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer.  Proc Natl Acad Sci USA. 2000;  97 13275-13280
• 17 Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois R N. Cyclooxygenase regulates angiogenesis induced by colon cancer cells.  Cell. 1998;  93 705-716
• 18 Chan T A, Morin P J, Vogelstein B, Kinzler K W. Mechanisms underlying nonsteroidal antiinflammatory drug-mediated apoptosis.  Proc Natl Acad Sci USA. 1998;  95 681-686
• 19 Hannun Y A. Functions of ceramide in coordinating cellular responses to stress.  Science. 1996;  274 1855-1859
• 20 Scorrano L, Penzo D, Petronilli V, Pagano F, Bernardi P. Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha aopototic signaling.  J Biol Chem. 2001;  276 12 035-12 040
• 21 Thun M J, Namboodiri M M, Heath C W. Aspirin use and reduced risk of fatal colon cancer.  N Engl J Med. 1991;  325 1593-1596
• 22 Giovannucci E, Egan K M, Hunter D J, Stampfer M J, Colditz G A, Willett W C, Speizer F E. Aspirin and the risk of colorectal cancer in women.  N Engl J Med. 1995;  333 609-614
• 23 Meade E A, Smith W L, DeWitt D L. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs.  J Biol Chem. 1993;  268 6610-6614
• 24 Patrono C, Patrignani P, Garcia Rodriguez L A. Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs.  J Clin Invest. 2001;  108 7-13
• 25 Xu X M, Sansores-Garcia L, Chen X M, Matijevic-Aleksic N, Du M, Wu K K. Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate.  Proc Natl Acad Sci USA. 1999;  96 5292-5297
• 26 Wu J, Xia H H, Tu S P, Fan D M, Lin M C, Kung H F, Lam S K, Wong B C. 15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer.  Carcinogenesis. 2003;  24 243-247
• 27 Grilli M, Pizzi M, Memo M, Spano P. Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation.  Science. 1996;  274 1383-1385
• 28 He T C, Chan T A, Vogelstein B, Kinzler K W. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.  Cell. 1999;  99 335-345
• 29 Huls G, Koornstra J J, Kleibeuker J H. Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas.  Lancet. 2003;  362 230-232
• 30 Dihlmann S, Klein S, Doeberitz M K. Reduction of beta-Catenin/T-Cell Transcription Factor Signaling by Aspirin and Indomethacin Is Caused by an Increased Stabilization of Phosphorylated beta-Catenin.  Mol Cancer Ther. 2003;  2 509-516
• 31 Awtry E H, Loscalzo J. Aspirin.  Circulation. 2000;  101 1206-1218
• 32 Amann R, Peskar B A. Anti-inflammatory effects of aspirin and sodium salicylate.  Eur J Pharmacol. 2002;  447 1-9
• 33 Pinczowski D, Ekbom A, Baron J, Yuen J, Adami H O. Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study.  Gastroenterology. 1994;  107 117-120
• 34 Moody G A, Jayanthi V, Probert C S, MacKay H, Mayberry J F. Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire.  Eur J Gastroenterol Hepatol. 1996;  8 1179-1183
• 35 Reinacher-Schick A, Schoeneck A, Graeven U, Schwarte-Waldhoff I, Schmiegel W. Mesalazine causes a mitotic arrest and induces caspase-dependent apoptosis in colon carcinoma cells.  Carcinogenesis. 2003;  24 443-451
• 36 Allgayer H. Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.  Aliment Pharmacol Ther. 2003;  18 10-14 (Suppl 2)
• 37 Bus P J, Nagtegaal I D, Verspaget H W, Lamers C B, Geldof H, Van Krieken J H, Griffioen G. Mesalazine-induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era?.  Aliment Pharmacol Ther. 1999;  13 1397-1402
• 38 Levin B. Potential pitfalls in the use of surrogate endpoints in colorectal adenoma chemoprevention.  J Natl Cancer Inst. 2003;  95 697-699
• 39 Levi F, Lucchini F, Negri E, La Vecchia C. Worldwide patterns of cancer mortality 1990 - 94.  Eur J Cancer Prev. 1999;  8 381-400
• 40 Steering Committee of the Physicians’ Health Study Research Group . Final report on the aspirin component of the ongoing Physicians’ Health Study.  N Engl J Med. 1989;  321 129-135
• 41 Imperiale T F. Aspirin and the prevention of colorectal cancer.  N Engl J Med. 2003;  348 879-880
• 42 Suleiman S, Rex D K, Sonnenberg A. Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis.  Gastroenterology. 2002;  122 78-84
• 43 Subbaramaiah K, Hart J C, Norton L, Dannenberg A J. Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways.  J Biol Chem. 2000;  275 14 838-14 845
• 44 Kune G A, Kune S, Watson L F. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study.  Cancer Res. 1988;  48 4399-4404
• 45 Rosenberg L, Palmer J R, Zauber A G, Warshauer M E, Stolley P D, Shapiro S. A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of largebowel cancer.  J Natl Cancer Inst. 1991;  83 355-358
• 46 Suh O, Mettlin C, Petrelli N J. Aspirin use, cancer, and polyps of the large bowel.  Cancer. 1993;  72 1171-1177
• 47 Muscat J E, Stellman S D, Wynder E L. Nonsteroidal antiinflammatory drugs and colorectal cancer.  Cancer. 1994;  74 1847-1854
• 48 Peleg I I, Maibach H T, Brown S H, Wilcox C M. Aspirin and nonsteroidal antiinflammatory drug use and the risk of subsequent colorectal cancer.  Arch Intern Med. 1994;  154 394-399
• 49 Reeves M J, Newcomb P A, Trentham-Dietz A, Storer B E, Remington P L. Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women.  Cancer Epidemiol Biomarkers Prev. 1996;  5 955-960
• 50 La Vecchia C, Negri E, Franceschi S, Conti E, Montella M, Giacosa A, Falcini A, Decarli A. Aspirin and colorectal cancer.  Br J Cancer. 1997;  76 675-677
• 51 Rosenberg L, Louik C, Shapiro S. Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma.  Cancer. 1998;  82 2326-2333
• 52 Friedman G D, Coates A O, Potter J D, Slattery M L. Drugs and colon cancer.  Pharmacoepidemiol Drug Safety. 1998;  7 99-106
• 53 Neugut A I, Rosenberg D J, Ahsan H, Jacobson J S, Wahid N, Hagan M, Rahman M I, Khan Z R, Chen L, Pablos-Mendez A, Shea S. Association between coronary heart disease and cancers of the breast, prostate, and colon.  Cancer Epidemiol Biomarkers Prev. 1998;  7 869-873
• 54 Paganini-Hill A, Chao A, Ross R K, Henderson B E. Aspirin use and chronic diseases: a cohort study of the elderly.  Bmj. 1989;  299 1247-1250
• 55 Thun M J, Namboodiri M M, Calle E E, Flanders W D, Heath C W. Aspirin use and risk of fatal cancer.  Cancer Res. 1993;  53 1322-1327
• 56 Schreinemachers D M, Everson R B. Aspirin use and lung, colon, and breast cancer incidence in a prospective study.  Epidemiology. 1994;  5 138-146
• 57 Giovannucci E, Rimm E B, Stampfer M J, Colditz G A, Ascherio A, Willett W C. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals.  Ann Intern Med. 1994;  121 241-246
• 58 Bosetti C, Gallus S, La Vecchia C. Aspirin and cancer risk: an update to 2001.  Eur J Cancer Prev. 2002;  11 535-542
• 59 Harris R E, Namboodiri K K, Farrar W B. Nonsteroidal antiinflammatory drugs and breast cancer.  Epidemiology. 1996;  7 203-205
• 60 Coogan P F, Rao S R, Rosenberg L, Palmer J R, Strom B L, Zauber A G, Stolley P D, Shapiro S. The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer.  Prev Med. 1999;  29 72-76
• 61 Friedman G D, Ury H K. Initial screening for carcinogenicity of commonly used drugs.  J Natl Cancer Inst. 1980;  65 723-733
• 62 Egan K M, Stampfer M J, Giovannucci E, Rosner B A, Colditz G A. Prospective study of regular aspirin use and the risk of breast cancer.  J Natl Cancer Inst. 1996;  88 988-993
• 63 Harris R E, Kasbari S, Farrar W B. Prospective study of nonsteoridal antiinflammatory drugs and breast cancer.  Oncol Rep. 1999;  6 71-73
• 64 Tzonou A, Polychronopoulou A, Hsieh C C, Rebelakos A, Karakatsani A, Trichopoulos D. Hair dyes, analgesics, tranquilizers and perineal talc application as risk factors for ovarian cancer.  Int J Cancer. 1993;  55 408-410
• 65 Cramer D W, Harlow B L, Titus-Ernstoff L, Bohlke K, Welch W R, Greenberg E R. Over-the-counter analgesics and risk of ovarian cancer.  Lancet. 1998;  351 104-107
• 66 Tavani A, Gallus S, La Vecchia C, Conti E, Montella M, Franceschi S. Aspirin and ovarian cancer: an Italian case-control study.  Ann Oncol. 2000;  11 1171-1173
• 67 Rosenberg L, Palmer J R, Rao R S, Coogan P F, Strom B L, Zauber A G, Stolley P D, Shapiro S. A case-control study of analgesic use and ovarian cancer.  Cancer Epidemiol Biomarkers Prev. 2000;  9 933-937
• 68 Moysich K B, Mettlin C, Piver M S, Natarajan N, Menezes R J, Swede H. Regular use of analgesic drugs and ovarian cancer risk.  Cancer Epidemiol Biomarkers Prev. 2001;  10 903-906
• 69 Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, Kato I, Koenig K L, Shore R E. Aspirin and epithelial ovarian cancer.  Prev Med. 2001;  33 682-687
• 70 Leitzmann M F, Stampfer M J, Ma J, Chan J M, Colditz G A, Willett W C, Giovannucci E. Aspirin use in relation to risk of prostate cancer.  Cancer Epidemiol Biomarkers Prev. 2002;  11 1108-1111
• 71 Farrow D C, Vaughan T L, Hansten P D, Stanford J L, Risch H A, Gammon M D, Chow W H, Dubrow R, Ahsan H, Mayne S T, Schoenberg J B, West A B, Rotterdam H, Fraumeni J F, Blot W J. Use of aspirin and other 10 nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.  Cancer Epidemiol Biomarkers Prev. 1998;  7 97-102
• 72 Sharp L, Chilvers C E, Cheng K K, McKinney P A, Logan R F, Cook-Mozaffari P, Ahmed A, Day N E. Risk factors for squamous cell carcinoma of the oesophagus in women: a case-control study.  Br J Cancer. 2001;  85 1667-1670
• 73 Funkhouser E M, Sharp G B. Aspirin and reduced risk of esophageal carcinoma.  Cancer. 1995;  76 1116-1119
• 74 Akre K, Ekstrom A M, Signorello L B, Hansson L E, Nyren O. Aspirin and risk for gastric cancer: a population-based case-control study in Sweden.  Br J Cancer. 2001;  84 965-968
• 75 Anderson K E, Johnson T W, Lazovich D, Folsom A R. Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer.  J Natl Cancer Inst. 2002;  94 1168-1171