Erfahrungsheilkunde 2003; 52(11): 724-732
DOI: 10.1055/s-2003-44308
Originalia

Karl F. Haug Verlag, in: MVS Medizinverlage Stuttgart GmbH & Co. KG

Präventive Maßnahmen gegen Prostatakrebs

Hoffnung und RealitätKarl-Friedrich Klippel, Ben L. Pfeifer
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
19. November 2003 (online)

Zusammenfassung

Vorbeugung von Prostatakrebs ist ein vordringliches gesundheitspolitisches Problem, da jedes Jahr mehr Männer mit dieser Erkrankung diagnostiziert werden. Die hohe Prävalenz und Inzidenzrate, eine lange Latenzperiode, und die signifikante Morbidität und Mortalität prädestinieren den Prostatakrebs zur Erforschung und Anwendung präventiver Maßnahmen. Voraussetzungen für die Entwicklung rationaler chemopräventiver Strategien gegen Prostatakrebs sind eine ausreichende Kenntnis der Karzinogenese, gut charakterisierte, potentiell präventive biologische und chemische Substanzen, geeignete Patientenkollektive zur Prüfung und verlässliche Biomarker zur Einschätzung des Krebswachstums. Die Wahl eines potentiell präventiven Mittels wird abhängen von experimentellen oder epidemiologischen Untersuchungen mit Effektivitätsnachweis, der Unbedenklichkeit des Mittels auch bei Langzeitanwendung, und einer rationalen Begründung bezüglich der zu erwartenden Aktivität. Berechtigte Hoffnung auf präventive Wirksamkeit bei Prostatakrebs besteht dabei für Antiandrogene und Antiöstrogene, 5-alpha-Reduktase Hemmer, Aromatase Hemmer, Retinoide, Vitamine D und E, Selen, Karotenoide, Soja Isoflavone, 2-Difluoromethylornithine, Lipoxygenase Hemmer, Apoptose Induktoren, und nicht-steroidale anti-entzündliche Medikamente. Einige dieser Substanzen sind gegenwärtig in der klinischen Prüfung Phase I-III.

Abstract

The increasing incidence rate for prostate cancer in the Western World combined with an ageing male population will create an enormous healthcare problem within the next 25 years. With its high prevalence, long latency, high incidence and significant morbidity and mortality, prostate cancer is an ideal target for chemoprevention. Developing rational chemopreventive strategies for prostate cancer requires in-depth knowledge of carcinogenesis, well-characterized agents, suitable cohorts, and reliable biomarkers of cancer. Choice of chemopreventive agent will depend on experimental or epidemiologic data demonstrating efficacy, good safety record with chronic administration, and a rationale for activity. Current promising agents include antiandrogens and antiestrogens, 5-alpha-reductase inhibitors, aromatase inhibitors, retinoids, vitamins D and E, selenium, carotenoids, soy isoflavones, 2-difluoromethylornithine, lipoxygenase inhibitors, apoptosis inducers, and nonsteroidal anti-inflammatory drugs. Several of these agents are now under evaluation in clinical trials phase 1, 2, and 3.

Literatur

  • 001 Scardino P T. The Prevention of Prostate Cancer - The Dilemma Continues.  N Engl J Med. 2003;  349 (3) 295-97
  • 002 Feigl P. et al . Design of the Prostate Cancer Prevention Trial (PCPT).  Control Clin Trials. 1995;  16 (3) 150-63
  • 003 Thompson I M. et al . The Influence of Finasteride on the Development of Prostate Cancer.  N Engl J Med. 2003;  349 (3) 213-22
  • 004 Tarle M. et al . Early diagnosis of prostate cancer in finasteride treated BPH patients.  Anticancer Res. 2003;  23 (1B) 693-6
  • 005 Kaplan S A. et al . PSA response to finasteride challenge in men with a serum PSA greater than 4 ng/ml and previous negative prostate biopsy: preliminary study.  Urology. 2002;  60 (3) 464-8
  • 006 Morrissey C, Watson R W. Phytoestrogens and prostate cancer.  Curr Drug Targets. 2003;  4 (3) 231-41
  • 007 Hebert J R. et al . Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study.  J Natl Cancer Inst. 1998;  90 (21) 1637-47
  • 008 Griffiths K, Morton M S, Denis L. Certain aspects of molecular endocrinology that relate to the influence of dietary factors on the pathogenesis of prostate cancer.  Eur Urol. 1999;  35 (5-6) 443-55
  • 009 Andersson S O. et al . Body size and prostate cancer: A 20-year follow-up study among 135006 Swedish construction workers.  J Natl Cancer Inst. 1997;  89 (5) 385-9
  • 010 Kristal A R, Cohen J H, Qu P, Stanford J L. Associations of energy, fat, calcium, and vitamin D with prostate cancer risk.  Cancer Epidemiol Biomarkers Prev. 2002;  11 (8) 719-25
  • 011 Hursting S D, Thornquist M, Henderson M M. Types of dietary fat and the incidence of cancer at five sites.  Prev Med. 1990;  19 (3) 242-53
  • 012 Berrigan D. et al . Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice.  Carcinogenesis. 2002;  23 (5) 817-22
  • 013 Hsing A W, Tsao L, Devesa S S. International trends and patterns of prostate cancer incidence and mortality.  Int J Cancer. 2000;  85 (1) 60-7
  • 014 Denis L, Morton M S, Griffiths K. Diet and its preventive role in prostatic disease.  Eur Urol. 1999;  35 (5-6) 377-87
  • 015 Moyad M A. Dietary fat reduction to reduce prostate cancer risk: controlled enthusiasm, learning a lesson from breast or other cancers, and the big picture.  Urology. 2002;  59 (4 Suppl 1) 51-62
  • 016 Hanash K A. et al . Prostatic carcinoma: a nutritional disease? Conflicting data from the Kingdom of Saudi Arabia.  J Urol. 2000;  164 (5) 1570-2
  • 017 Kolonel L N. Fat, meat, and prostate cancer.  Epidemiol Rev. 2001;  23 (1) 72-81
  • 018 Michaud D S. et al . A prospective study on intake of animal products and risk of prostate cancer.  Cancer Causes Control. 2001;  12 (6) 557-67
  • 019 Bosland M C, Oakley-Girvan I, Whittemore A S. Dietary fat, calories, and prostate cancer risk.  J Natl Cancer Inst. 1999;  91 (6) 489-91
  • 020 Saez E. et al . Activators of the nuclear receptor PPARgamma enhance colon polyp formation.  Nat Med. 1998;  4 (9) 1058-61
  • 021 Ghosh J, Myers C E. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells.  Proc Natl Acad Sci USA. 1998;  27; 95 (22) 13182-7
  • 022 Chan J M. et al . Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden).  Cancer Causes Control. 1998;  9 (6) 559-66
  • 023 Zock P L, Katan M B. Linoleic acid intake and cancer risk: a review and meta-analysis.  Am J Clin Nutr. 1998;  68 (1) 142-53
  • 24 Willett W C. Specific fatty acids and risks of breast and prostate cancer: dietary intake.  Am J Clin Nutr. 1997;  66 (S 6) 1557S-63S
  • 025 Godley P A. et al . Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma.  Cancer Epidemiol Biomarkers Prev. 1996;  5 (11) 889-95
  • 026 Baylin A. et al . Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica.  Circulation. 2003;  107 (12) 1586-91
  • 027 Renaud S, Lanzmann-Petithory D. Dietary fats and coronary heart disease pathogenesis.  Curr Atheroscler Rep. 2002;  4 (6) 419-24
  • 028 Newcomer L M. et al . The association of fatty acids with prostate cancer risk.  Prostate. 2001;  47 (4) 262-8
  • 029 Giovannucci E. et al . A prospective study of dietary fat and risk of prostate cancer.  J Natl Cancer Inst. 1993;  85 (19) 1571-9
  • 030 Kolonel L N. et al . Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study.  Cancer Epidemiol Biomarkers Prev. 2000;  9 (8) 795-804
  • 031 Faucher K. et al . Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges.  Biochimie. 2003;  85 (6) 611-7
  • 032 Duffield-Lillico A J. et al . Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial.  BJU Int. 2003;  91 (7) 608-12
  • 033 Clark L C. et al . Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial.  Br J Urol. 1998;  81 (5) 730-4
  • 034 Clark L C. 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 (24) 1957-63
  • 035 Yoshizawa K. et al . Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer.  J Natl Cancer Inst. 1998;  90 (16) 1219-24
  • 036 Heinonen O P. et al . Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.  J Natl Cancer Inst. 1998;  90 (6) 440-6
  • 037 Moyad M A. Selenium and vitamin E supplements for prostate cancer: evidence or embellishment?.  Urology. 2002;  59 (4 Suppl 1) 9-19
  • 038 Klein E A. et al . SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design.  Prostate Cancer Prostatic Dis. 2000;  3 (3) 145-51
  • 039 Liao S. The medicinal action of androgens and green tea epigallocatechin gallate.  Hong Kong Med J. 2001;  7 (4) 369-74
  • 040 Adhami V M, Ahmad N, Mukhtar H. Molecular targets for green tea in prostate cancer prevention.  J Nutr. 2003;  133 (7) 2417S-24S
  • 041 Agarwal R. Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.  Biochem Pharmacol. 2000;  60 (8) 1051-9
  • 042 Gupta S, Hussain T, Mukhtar H. Molecular pathway for epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells.  Arch Biochem Biophys. 2003;  410 (1) 177-85
  • 043 Gupta S, Ahmad N, Nieminen A L, Mukhtar H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells.  Toxicol Appl Pharmacol. 2000;  164 (1) 82-90
  • 044 Meydani M. Nutrition interventions in aging and age-associated disease.  Ann N Y Acad Sci. 2001;  928 226-35
  • 045 Liao S. et al . Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate.  Cancer Lett. 1995;  96 (2) 239-43
  • 046 Gupta S. et al . Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols.  Proc Natl Acad Sci USA. 2001;  98 (18) 10350-5
  • 047 Kim L, Rao A V, Rao L G. Effect of Lycopene on Prostate LNCaP Cancer Cells in Culture.  J Med Food. 2002;  5 (4) 181-7
  • 048 Heber D, Lu Q Y. Overview of mechanisms of action of lycopene.  Exp Biol Med (Maywood). 2002;  227 (10) 920-3
  • 049 Bowen P. et al . Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis.  Exp Biol Med (Maywood). 2002;  227 (10) 886-93
  • 050 Weisburger J H. Lycopene and tomato products in health promotion.  Exp Biol Med (Maywood). 2002;  227 (10) 924-7
  • 051 von Holtz R L, Fink C S, Awad A B. Beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells.  Nutr Cancer. 1998;  32 (1) 8-12
  • 052 Awad A B. et al . In vitro and in vivo (SCID mice) effects of phytosterols on the growth and dissemination of human prostate cancer PC-3 cells.  Eur J Cancer Prev. 2001;  10 (6) 507-13
  • 053 Bouic P J. et al . Beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory vitamin combination.  Int J Immunopharmacol. 1996;  18 (12) 693-700
  • 054 Nelson W G, DeWeese T L, DeMarzo A M. The diet, prostate inflammation, and the development of prostate cancer.  Cancer Metastasis Rev. 2002;  21 (1) 3-16
  • 055 Brooks J D, Paton V G, Vidanes G. Potent induction of phase 2 enzymes in human prostate cells by sulforaphane.  Cancer Epidemiol Biomarkers Prev. 2001;  10 (9) 949-54
  • 056 Chiao J W. et al . Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells.  Int J Oncol. 2002;  20 (3) 631-6
  • 057 Cohen J H, Kristal A R, Stanford J L. Fruit and vegetable intakes and prostate cancer risk.  J Natl Cancer Inst. 2000;  92 (1) 61-8
  • 058 Kim I Y. et al . Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines.  Cancer Res. 2002;  62 (18) 5365-9
  • 059 Nanni S. et al . Signaling through estrogen receptors modulates telomerase activity in human prostate cancer.  J Clin Invest. 2002;  110 (2) 219-27
  • 060 Steiner M S, Raghow S. Antiestrogens and selective estrogen receptor modulators reduce prostate cancer risk.  World J Urol. 2003;  21 (1) 31-6
  • 061 Stein S. et al . Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial.  Am J Clin Oncol. 2001;  24 (3) 283-5
  • 062 Gupta S. et al . Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma.  Prostate. 2000;  42 (1) 73-8
  • 063 Moran E M. Epidemiological and clinical aspects of nonsteroidal anti-inflammatory drugs and cancer risks.  J Environ Pathol Toxicol Oncol. 2002;  21 (2) 193-201
  • 064 Lieberman R. Evolving strategies for prostate cancer chemoprevention trials.  World J Urol. 2003;  21 3-8
  • 065 Krishnan A V, Peehl D M, Feldman D. Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression.  J Cell Biochem. 2003;  88 (2) 363-71
  • 066 Sung V, Feldman D. 1,25-Dihydroxyvitamin D3 decreases human prostate cancer cell adhesion and migration.  Mol Cell Endocrinol. 2000;  164 (1-2) 133-43
  • 067 Ahonen M H. et al . Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland).  Cancer Causes Control. 2000;  11 (9) 847-52
  • 068 Beer T M. et al . Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer.  J Clin Oncol. 2003;  21 (1) 123-8
  • 069 Platz E A. et al . Racial variation in prostate cancer incidence and in hormonal system markers among male health professionals.  J Natl Cancer Inst. 2000;  92 (24) 2009-17
  • 070 Wu A H. et al . Lifestyle determinants of 5alpha-reductase metabolites in older African-American, white, and Asian-American men.  Cancer Epidemiol Biomarkers Prev. 2001;  10 (5) 533-8
  • 071 Woodson K. et al . Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites.  Prostate. 2003;  55 (5) 199-205
  • 072 Elkins D A. et al . Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer.  Prostate. 2003;  56 (1) 30-6
  • 073 Gong G. et al . Segregation analysis of prostate cancer in 1,719 white, African-American and Asian-American families in the United States and Canada.  Cancer Causes Control. 2002;  13 (5) 471-82
  • 074 Cotter M P. et al . Role of family history and ethnicity on the mode and age of prostate cancer presentation.  Prostate. 2002;  50 (4) 216-21
  • 075 Andersson S O. et al . Lifestyle factors and prostate cancer risk: a case-control study in Sweden.  Cancer Epidemiol Biomarkers Prev. 1996;  5 (7) 509-13
  • 076 Wannamethee S G, Shaper A G, Walker M. Physical activity and risk of cancer in middle aged men.  Br J Cancer. 2001;  85 1311-16
  • 077 Thune I, Lund E. Physical activity and risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men.  Cancer Causes and Control. 1994;  5 549-56
  • 078 Oliveria S A. et al . The association between cardiorespiratory fitness and prostate cancer.  Med Sci Sports Exerc. 1996;  28 97-104
  • 079 Hartmann T J. et al . Physical activity and prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (Finnland).  Cancer Causes and Control. 1998;  9 11-18
  • 080 Clarke G, Whittemore A S. Prostate cancer risk in relation to anthropometry and physical activity: National Health and Nutrition Examination Survey I Epidemiological Follow-Up Study.  Cancer Epidemiol Biomarkers Prev. 2000;  9 875-81
  • 081 Liu S. et al . A prospective study of physical activity and risk of prostate cancer in US physicians.  Int J Epidemiol. 2000;  29 29-35
  • 082 Lee I M, Sesso H D, Paffenberger R S. A prospective cohort study of physical activity and body size in relation to prostate cancer risk (United States).  Cancer Causes and Control. 2001;  12 187-93
  • 083 Sung J F C. et al . Risk factors for prostate cancinoma in Taiwan.  Cancer. 1999;  86 484-91
  • 084 Cerhan J R. et al . Association of smoking, body mass and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States).  Cancer Causes and Control. 1997;  8 229-38
  • 085 Hackney A C. The male reproductive system and endurance exercise.  Med Sci Sports Exerc. 1996;  28 180-89
  • 086 Yan H. et al . Effect of moderate exercise on immune senescence in men.  Eur J Appl Physiol. 2001;  86 105-11
  • 087 Lund Nilsen T I, Johnsen R, Vatten L J. Socio-economic and lifestyle factors associated with the risk of prostate cancer.  Br J Cancer. 2000;  82 (7) 1358-63
  • 088 Kobrinsky N L. et al . Impact of smoking on cancer stage at diagnosis.  J Clin Oncol. 2003;  21 (5) 907-13
  • 089 Wang C Y. et al . Correlation of the genotypes for N-acetyltransferases 1 and 2 with double bladder and prostate cancers in a case-comparison study.  Anticancer Res.. 2002;  22 (6B) 3529-35
  • 090 Roberts W w, Platz E A, Walsh P C. Association of cigarette smoking with extraprostatic prostate cancer in young men.  J Urol. 2003;  169 (2) 512-6
  • 091 Sharpe C R, Siemiatycki J. Joint effects of smoking and body mass index on prostate cancer risk.  Epidemiology. 2001;  12 (5) 546-51
  • 092 Sharpe C R, Siemiatycki J. Case-control study of alcohol consumption and prostate cancer risk in Montreal, Canada.  Cancer Causes Control. 2001;  12 (7) 589-98
  • 093 Sesso H D, Paffenbarger Jr R S, Lee I M. Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study.  Int J Epidemiol. 2001;  30 (4) 749-55
  • 094 Albertsen K, Gronbaek M. Does amount or type of alcohol influence the risk of prostate cancer?.  Prostate. 2002;  52 (4) 297-304
  • 095 Mills P K. et al . Cancer incidence among California Seventh-Day Adventists, 1976-1982.  Am J Clin Nutr. 1994;  59 (S 5) 1136S-1142S
  • 096 Dennis L K, Lynch C F, Torner J C. Epidemiologic association between prostatitis and prostate cancer.  Urology. 2002;  60 (1) 78-83
  • 097 Dennis L K, Dawson D V. Meta-analysis of measures of sexual activity and prostate cancer.  Epidemiology. 2002;  13 (1) 72-9
  • 098 Hayes R B. et al . Sexual behaviour, STDs and risks for prostate cancer.  Br J Cancer. 2000;  82 (3) 718-25
  • 099 Rosenblatt K A, Wicklund K g, Stanford J L. Sexual factors and the risk of prostate cancer.  Am J Epidemiol. 2001;  153 (12) 1152-8
  • 100 Emard J F. et al . Vasectomy and prostate cancer in Quebec, Canada.  Health Place. 2001;  7 (2) 131-9
  • 101 Dennis L K, Dawson D V, Resnick M I. Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy status, age at vasectomy, and time since vasectomy.  Prostate Cancer Prostatic Dis. 2002;  5 (3) 193-203
  • 102 DeAntoni E P. et al . A cross-sectional study of vasectomy, time since vasectomy and prostate cancer.  Prostate Cancer Prostatic Dis. 1997;  1 (2) 73-78
  • 103 Cox B. et al . Vasectomy and risk of prostate cancer.  JAMA. 2002;  287 (23) 3110-5
  • 104 Chacko Jaet. et al . Vasectomy and prostate cancer characteristics of patients referred for prostate biopsy.  J Urol. 2002;  168 1408-11
  • 105 Saxe G A. et al . Can diet in conjunction with stress reduction affect the rate of increase in prostate specific antigen after biochemical recurrence of prostate cancer?.  J Urol. 2001;  166 (6) 2202-7

Korrespondenzautoren:

Prof. Dr. Dr. med. Ben L. Pfeifer

Direktor für Klinische Forschung
Aeskulap Klinik

Gersauer Strasse 8

CH-6440 Brunnen

Schweiz

Prof. Dr. med. Karl-Friedrich Klippel

Urologische Klinik
Akademisches Lehrkrankenhaus Celle

Deutschland

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