Zusammenfassung
Ein wichtiger Baustein zur Evidenz, die den Einsatz von Ernährungssubstanzen in der
Krebsprophylaxe nahe legt, sind doppelblind angelegte randomisierte lnterventionsstudien,
die eine Risikosenkung beim Einsatz der zu untersuchenden Substanz im Vergleich zu
einer Plazebosubstanz an dem Zielkrankheitsbild, hier Krebserkrankung, nachweisen.
Gleichzeitig können diese Studien zusätzlich den Nachweis erbringen, dass das Risiko
für andere Krankheitsbilder nicht erhöht ist. Im Rahmen der Primärprophylaxe gibt
es neben vier größeren abgeschlossenen lnterventionsstudien mit 20 000 bis 30 000
Personen eine Reihe von kleineren Studien in der Größenordnung von 500 bis 3000 Personen,
die potenzielle krebsprophylaktische Substanzen aus dem Ernährungsbereich an Hochrisikogruppen
überprüft haben. In diesen Studien wurden Vitamin A, β-Karotin, Vitamin E, Selen und
Kalzium entweder als Reinsubstanz eingesetzt oder in unterschiedlichen Kombinationen,
zum Teil auch mit anderen Substanzen. Im Bereich des Einsatzes von Reinsubstanzen
besaß bis auf Kalzium keine der Substanzen in Bezug auf die Primärhypothese eine risikoreduzierende
Wirkung. Kalzium reduzierte die Rekurrenz von Darmpolypen. Dieses Modell lässt jedoch
nur bedingt Rückschlüsse auf das Kolonkrebsrisiko zu. Auch im Bereich der überprüften
Sekundärhypothesen gab es viele „Null”-Ergebnisse zur Gesamtkrebsmortalität und einzelnen
Krebsformen. Bemerkenswerte Supplementierungseffekte konnten bei Selen und Vitamin
E für spezielle Krebserkrankungen beobachtet werden. Bei Selen wurden in einer kleineren
lnterventionsstudie risikosenkende Effekte für die Gesamtkrebsmortalität und speziell
für Lungen-, Prostata- und Kolonkrebs beobachtet. Die Supplementierung von Vitamin
E ergab eine Absenkung des Prostatakarzinomrisikos. Gleichzeitig hat diese Studie
ergeben, dass in der Vitamin-E-Supplementierungsgruppe das Risiko für einen hämorrhagischen
Schlaganfall angestiegen ist. Beide Ergebnisse bedürfen vor weiteren Schlussfolgerungen
der Überprüfung. β-Karotin ist die Substanz, die am häufigsten in lnterventionsstudien
zur Anwendung kam. Hier konnte festgestellt werden, dass bei Risikogruppen wie Rauchern
das Krebsrisiko ansteigt und in der nichtrauchenden Bevölkerung keine Effekte auf
das Krebsrisiko bei einer Supplementierung durch β-Karotin zu beobachten waren. Eine
lnterventionsstudie in Kolumbien erbrachte Hinweise, dass β-Karotin und Vitamin C
präkanzeröse Läsionen im Magen verstärkt zur Abheilung bringen können und so möglicherweise
das Magenkrebsrisiko verringern. Als Fazit ergibt sich, dass aus den lnterventionsstudien
für viele Einzelsubstanzen der Nachweis besteht, dass sie nicht krebsprophylaktisch
wirken und bei einigen der Hinweis, dass der (Zufalls-)Befund einer organspezifischen
Krebsrisikosenkung zunächst auf eine solide Basis gestellt werden muss.
Calcium and Antioxidants as Supplements in Cancer Prophylaxis - Status Report on Interventional
Studies
The evaluation of the use of single substances for cancer risk reduction should base
on the review of total evidence which should show unequivocal inference of its effectiveness.
An important part of the generation of evidence are double-blind randomised intervention
studies which demonstrate a reduction in risk in connection with the substance of
investigation compared to a placebo substance in correlation to a certain disease,
cancer. Such studies can also show i.e., in this case, that the risk for other diseases
is not increased. In cancer research antioxidative substances had been preferentially
investigated regarding their risk-reducing properties. In the area of primary prevention
the number of successfully completed double-blind randomised intervention studies
with cancer as endpoint or surrogate endpoint near to cancer such as the recurrence
of colon polyps is still limited. Aside from larger intervention studies with 20 000
to 30 000 study participants there are a number of smaller studies 500 to 3000 subjects
in size which tested potentially cancer risk reductive substances in high-risk groups.
Intervention studies with smaller numbers were not considered in this review due to
problems with the statistical significance and in addition such studies with surrogate
endpoints which had been far away from the actual tumour. Test substances had been
in particular vitamin A, β-carotene, vitamin E, selenium, and calcium. These substances
were applied either as pure substances or in different combinations. For each intervention
study first a primary hypothesis was formulated and subsequently various secondary
hypotheses, if at all, in the course of the study. With the exception of calcium none
of the substances showed risk-reducing effects in relation to the primary hypothesis.
Calcium was applied in the model of colon polyp recurrence that however, allows only
limited reference to the risk of colon cancer. Interesting results in the area of
the secondary hypothesis were found in relation to selenium and vitamin E. Risk-reducing
effects were observed for lung, prostate and colon cancer in a small intervention
study with selenium. This result requires further testing because the study design
is not well suited in the area of primary prevention and due to the small numbers
observed a further test in a larger study taking the normal population might be useful.
The supplementation of vitamin E resulted in reduction in risk for prostate cancer
in a large intervention study with vitamin E. This result, too, should be re-tested.
This study also showed that the risk of haemorrhagic stroke was increased in the group
with vitamin E supplementation. β-carotene is a substance which has been most tested
in intervention studies. For this substance it could be revealed that particular risk
groups such as smokers exhibit an increased lung cancer risk and in the non-smoking
population no effect on risk had been observed by supplementation with β-carotene.
An intervention study in Columbia observed that β-carotene and vitamin C support regression
of pre-cancerous lesions in the stomach and may in this way contribute to reduce the
risk of gastric cancer. lt can be concluded from the intervention studies that for
many dietary substances evidence exists that they do not reduce the risk of cancer
and for some of them that the result of an organ-specific reduction in risk needs
to be put on a solid basis.
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Dr. Heiner Boeing
Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Abteilung Epidemiologie
Arthur-Scheunert-Allee 114 - 116
14558 Bergholz-Rehbrücke
eMail: boeing@www.dife.de
