Download PDF
Z Gastroenterol 2002; 40(S2): 79-83
DOI: 10.1055/s-2002-35886
Supplement
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

Das Kolonkarzinom - eine vermeidbare Erkrankung?

Strategien zur ChemopräventionT. Seufferlein, G. Adler
  • 1Abt. Innere Medizin I, Medizinische Universitätsklinik Ulm
Further Information

Publication History

Publication Date:
04 December 2002 (online)

Also available at
   Permissions and Reprints
Preview

Folgende Abkürzungen werden im Text verwendet:

FAP: Familiäre adenomatöse Polyposis
IKK: IkB Kinase
MSI: Mikrosatelliteninstabilität
NSAR: Nicht steroidale Antirheumatika
PPAR: Peroxisome proliferator-activated receptor

Ein entscheidender Durchbruch im Verständnis von Tumorerkrankungen gelang durch die Erkenntnis, dass sich die Entstehung von Tumoren in mehrere Entwicklungsphasen unterteilen lässt. Durch Akkumulation initialer, primärer und sekundärer Mutationen in Onkogenen oder Tumorsuppressorgenen kommt es in mehreren Schritten zur Entwicklung von Karzinomen. Ein Modell für das Kolonkarzinom, die Adenom-Karzinom-Sequenz, wurde von Vogelstein und Kinzler entwickelt, ähnliche Modelle gibt es mittlerweile z. B. auch für das Pankreaskarzinom. Im Falle des Kolonkarzinoms dauert der Prozess bis zur Entstehung eines Karzinoms in der Regel 5-10 Jahre. Damit gewinnen Früherkennungsmaßnahmen wie z. B. die Koloskopie überragende Bedeutung. Möglicherweise besteht aber auch eine Chance, durch ­andere präventive Maßnahmen das (Wieder-)Auftreten von Karzinomen/Polypen wirksam zu verhindern. In dieser Übersicht wollen wir den gegenwärtigen Stand der Prävention gastro­intestinaler Tumoren durch pharmakologische Maßnahmen, aber auch durch Veränderungen von Lebensstil und Ernährung darstellen.

Literatur

  • 1 Evans R C, Fear S, Ashby D. et al . Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.  Gastroenterology. 2002;  122 1784-1792
    Search in Google Scholar
  • 2 Martinez M E, Giovannucci E, Spiegelman D. et al . Leisure-time physical activity, body size, and colon cancer in women.  Nurses’ Health Study Research Group J Natl Cancer Inst. 1997;  89 948-955
    Search in Google Scholar
  • 3 Shephard R J, Futcher R. Physical activity and cancer: how may protection be maximized?.  Crit Rev Oncog. 1997;  8 219-272
    Search in Google Scholar
  • 4 Michels K B, Giovannucci E, Joshipura K J. et al . Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers.  J Natl Cancer Inst. 2000;  92 1740-1752
    Search in Google Scholar
  • 5 Kono S, Hirohata T. Nutrition and stomach cancer.  Cancer Causes Control. 1996;  7 41-55
    Search in Google Scholar
  • 6 Botterweck A A, van den Brandt P A, Goldbohm R A. A prospective cohort study on vegetable and fruit consumption and stomach cancer risk in The Netherlands.  Am J Epidemiol. 1998;  148 842-853
    Search in Google Scholar
  • 7 Fuchs C S, Willett W C, Colditz G A. et al . The influence of folate and multivitamin use on the familial risk of colon cancer in women.  Cancer Epidemiol Biomarkers Prev. 2002;  11 227-234
    Search in Google Scholar
  • 8 Willett W C. Diet and Cancer.  The Oncologist. 2000;  5 393-404
    Search in Google Scholar
  • 9 Baron J A, Beach M, Mandel J S. et al . Calcium Supplements for the Prevention of Colorectal Adenomas.  N Engl J Med. 1999;  340 101-107
    Search in Google Scholar
  • 10 Garland C F, Garland F C, Gorham E D. Calcium and Vitamin D: Their Potential Roles in Colon and Breast Cancer Prevention Ann.  N.Y. Acad. Sci. 1999;  889 107-119
    Search in Google Scholar
  • 11 Wu K, Willett W C, Fuchs C S. et al . Calcium Intake and Risk of Colon Cancer in Women and Men.  J Natl Cancer Inst. 2002;  94 437-446
    Search in Google Scholar
  • 12 Hyman J, Baron J A, Dain B J. et al . Dietary and supplemental calcium and the recurrence of colorectal adenomas.  Cancer Epidemiol Biomarkers Prev. 1998;  7 291-295
    Search in Google Scholar
  • 13 Giovannucci E, Rimm E B, Stampfer M J. et al . Intake of fat, meat, and fiber in relation to risk of colon cancer in men.  Cancer Res. 1994;  54 2390-2397
    Search in Google Scholar
  • 14 Goldbohm R A, van den Brandt P A, van ‘t V eer P. et al . A prospective cohort study on the relation between meat consumption and the risk of colon cancer.  Cancer Res. 1994a;  54 718-723
    Search in Google Scholar
  • 15 et al . Kampman E, Slattery ML, Bigler J.  Meat Consumption, Genetic Susceptibility, and Colon Cancer Risk: A United States Multicenter Case-Control Study Cancer Epidemiol Biomarkers Prev. 1999;  8 15-24
    Search in Google Scholar
  • 16 Thun M J, Calle E E, Namboodiri M M. et al . Risk factors for fatal colon cancer in a large prospective study.  J Natl Cancer Inst. 1992;  84 1491-1500
    Search in Google Scholar
  • 17 Willett W C, Stampfer M J, Colditz G A. et al . Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.  N Engl J Med. 1990;  323 1664-1672
    Search in Google Scholar
  • 18 Bartsch H, Nair J, Owen R W. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers.  Carcinogenesis. 1999;  20 2209-2218
    Search in Google Scholar
  • 19 Garfinkel L. Overweight and mortality.  Cancer. 1986;  58 1826-1829
    Search in Google Scholar
  • 20 Giovannucci E, Colditz G A, Stampfer M J. et al . Physical activity, obesity, and risk of colorectal adenoma in woman (United States).  Cancer Causes Control. 1996;  7 253-263
    Search in Google Scholar
  • 21 Fuchs C S, Willett W C, Colditz G A. et al . The influence of folate and multivitamin use on the familial risk of colon cancer in women.  Cancer Epidemiol Biomarkers Prev. 2002;  11 227-234
    Search in Google Scholar
  • 22 Goldbohm R A, Van den Brandt P A, Van ‘t P Veer. et al . Prospective study on alcohol consumption and the risk of cancer of the colon and rectum in the Netherlands.  Cancer Causes Control. 1994b;  5 95-104
    Search in Google Scholar
  • 23 Potter J D. Nutrition and colorectal cancer.  Cancer Causes Control. 1996;  7 127-146
    Search in Google Scholar
  • 24 Tavani A, Pregnolato A, La V ecchia C. Coffee and tea intake and risk of cancers of the colon and rectum: a study of 3,530 cases and 7,057 controls.  Int J Cancer. 1997;  73 193-197
    Search in Google Scholar
  • 25 Kim I Y, Baik H W, Fawaz K. et al . Effects of folate supplementation on two provisional molecular makers: a prospective, randomized trail. .  Am J Gastroenterol. 2001;  96 184-195
    Search in Google Scholar
  • 26 Giovannucci E, Rimm E B, Ascherio A. et al . Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men.  J Natl Cancer Inst. 1995;  87 265-273
    Search in Google Scholar
  • 27 Fuchs C S, Willett W C, Colditz G A. et al . The influence of folate and multivitamin use on the familial risk of colon cancer in women.  Cancer Epidemiol Biomarkers Prev. 2002;  11 227-234
    Search in Google Scholar
  • 28 Giovannucci V, Stampfer M J, Colditz G A. et al . Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study.  Ann Intern Med. 1998;  129 517-524
    Search in Google Scholar
  • 29 White E, Shannon J S, Patterson R E. Relationship between vitamin and calcium supplement use and colon cancer.  Cancer Epidemiol Biomarkers Prev. 1997;  6 769-774
    Search in Google Scholar
  • 30 Giovannucci V, Stampfer M J, Colditz G A. et al . Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study.  Ann Intern Med. 1998;  129 517-524
    Search in Google Scholar
  • 31 Clark L C, Combs G F Jr, Turnbull B W. et al . Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.  JAMA. 1996;  276 1957-1963
    Search in Google Scholar
  • 32 Ghadirian P, Maisonneuve P, Perret C. et al . A case-control study of toenail selenium and cancer of the breast, colon, and prostate.  Cancer Detect Prev. 2000;  24 305-313
    Search in Google Scholar
  • 33 Willett W C. Diet and Cancer.  The Oncologist. 2000;  5 393-404
    Search in Google Scholar
  • 34 Levi F, Pasche C, Lucchini F. et al . Selected micronutrients and colorectal cancer. a case-control study from the canton of Vaud, Switzerland.  Eur J Cancer. 2000;  36 (16) 2115-2119
    Search in Google Scholar
  • 35 Heijnen M L, van Amelsvoort J M, Deurenberg P. et al . Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men Am.  J. Clinical Nutrition. 1998;  67 322-331
    Search in Google Scholar
  • 36 Hylla S, Gostner A, Dusel G. et al . Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention.  Am. J. Clinical Nutrition. 1998;  67 136-142
    Search in Google Scholar
  • 37 The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group . The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.  N Engl J Med. 1994;  330 1029-1035
    Search in Google Scholar
  • 38 Calle E E, Miracle-McMahill H L, Thun M J. et al . Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women.  J Natl Cancer Inst. 1995;  87 517-523
    Search in Google Scholar
  • 39 Grodstein F, Newcomb P A, Stampfer M J. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis.  Am J Med. 1999;  106 574-582
    Search in Google Scholar
  • 40 Slattery M L, Potter J D, Curtin K. et al . Estrogens Reduce and Withdrawal of Estrogens Increase Risk of Microsatellite Instability-positive Colon Cancer.  Cancer Res. 2001;  61 126-130
    Search in Google Scholar
  • 41 Morris C D, Armstrong G R, Bigley G. et al . Cyclooxygenase-2 expression in the BarrettŽs metaplasia-dysplasia-adenocarcinoma sequence.  Am J Gastroenterol. 2001;  96 990-996
    Search in Google Scholar
  • 42 Kokawa A, Kondo H, Gotoda T. et al . Increased expression of cyclooxgenase-2 in human pancreatic neoplasms and potential for chemoprevention by cyclooxygenase inhibitors.  Cancer. 2001;  91 333-338
    Search in Google Scholar
  • 43 Kawamori T, Rao C V, Seibert K. et al . Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis.  Cancer Res. 1998;  58 409-412
    Search in Google Scholar
  • 44 Jacoby R F, Seibert K, Cole C E. et al . The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis.  Cancer Res,. 2000;  60 5040-5044
    Search in Google Scholar
  • 45 Oshima M, Dinchuk J E, Kargman S L. et al . Suppression of intestinal polyposis in APC delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2).  Cell. 1996;  87 803-809
    Search in Google Scholar
  • 46 Giardiello F M, Hamilton S R, Krush A J. et al . Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis.  N Engl J Med. 1993;  328 1313-1316
    Search in Google Scholar
  • 47 Labayle D, Fischer D, Vielh P. et al . Sulindac causes regression of rectal polyps in familial adenomatous polyposis.  Gastroenterology. 1991;  101 635-639
    Search in Google Scholar
  • 48 Nugent K P, Farmer K C, Spigelman A D. et al . Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis.  Br J Surg. 1993;  80 1618-1619
    Search in Google Scholar
  • 49 Steinbach G, Lynch P M, Phillips R K. et al . The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.  N Engl J Med. 2000;  342 1946-1952
    Search in Google Scholar
  • 50 Giardiello F M, Yang V W, Hylind L M. et al . Primary chemoprevention of familial adenomatous polyposis with sulindac.  N Engl J Med. 2002;  346 (4) 1054-1059
    Search in Google Scholar
  • 51 Yin M J, Yamamoto Y, Gaynor R B. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta.  Nature. 1998;  396 77-80
    Search in Google Scholar
  • 52 Stark L A, Din F V, Zwacka R M. et al . Aspirin-induced activation of the NF-kappaB signaling pathway: a novel mechanism for aspirin-mediated apoptosis in colon cancer cells.  FASEB J. 2001;  15 1273-1275
    Search in Google Scholar
  • 53 Tegeder I, Pfeilschifter J, Geisslinger G. Cyclooxygenase-independent actions of cyclooxygenase inhibitors.  FASEB J. 2001;  15 2057-2072
    Search in Google Scholar
  • 54 Shimada T, Kojima K, Yoshiura K. et al .Characteristics of the peroxisome proliferator activated receptor nnn (PPARnnn) ligand induced apoptosis in colon cancer cells. Gut 2002 50: 658-664
    Search in Google Scholar
  • 55 Sarraf P, Mueller E, Smith W M. et al . Loss-of-function mutations in PPAR gamma associated with human colon cancer.  Mol Cell. 1999;  3 799-804
    Search in Google Scholar
  • 56 Gupta R A, Tan J, Krause W F. et al .Prostacyclin-mediated activation of peroxisome proliferator-activated recepor d in colorectal cancer. PNAS 2000 97: 13275-13280
    Search in Google Scholar
  • 57 Park B H, Vogelstein B, Kinzler K W. Genetic disruption of PPAR delta decreases the tumorigenicity of human colon cancer cells.  PNAS. 2001;  98 2598-2603
    Search in Google Scholar
  • 58 Zhang L, Yu J, Park B H. et al . Role of Bax in the apoptotic response to anticancer agents.  Science. 2000;  290 989-992
    Search in Google Scholar
  • 59 Zhou X M, Wong B C, Fan X M. et al . Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak.  Carcinogenesis. 2001;  22 1393-1397
    Search in Google Scholar
  • 60 Farrow D C, Vaughan T L, Hansten P D. et al . Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.  Cancer Epidemiol Biomarkers Prev. 1998;  7 97-102
    Search in Google Scholar
  • 61 Akre K, Ekstrom A M, Signorello L B. et al . Aspirin and risk for gastric cancer. A population-based case-control study in Sweden.  Br J Cancer. 2001;  84 965-968
    Search in Google Scholar
  • 62 Farrow D C, Vaughan T L, Hansten P D. et al . Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.  Cancer Epidemiol Biomarkers Prev. 1998;  7 97-102
    Search in Google Scholar
  • 63 Anderson K E, Johnson T W, Lazovich D. et al . Association Between Nonsteroidal Anti-Inflammatory Drug Use and the Incidence of Pancreatic Cancer JNCI.  2002;  94 1168-1171
    Search in Google Scholar
  • 64 Suleiman S, Rex D K, Sonnenberg A. Chemoprevention of colorectal cancer by aspirin: a cost-effectiveness analysis.  Gastroenterology. 2002;  122 78-84
    Search in Google Scholar
  • 65 Langman M J, Cheng K K, Gilman E A. et al . Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database.  BMJ. 2000;  320 1642-1646
    Search in Google Scholar

G. Adler

Abt. Innere Medizin I, Medizinische Universitätsklinik

Robert-Koch-Straße 8

89081 Ulm