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Observational epidemiological surveys (WG 3) page 45
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Comments on the results of the intervention trials
With the exception of a protective effect of β-carotene at 15mg in combination with vitamin E
at 30mg and Se at 50µg against gastric cancer in the main Linxian trial, which was borderline
significance and not confirmed in the ATBC study, none of the studies provided evidence of a
protective effect of β-carotene, alone or in combination with vitamin E or retinol. This is also
true for studies on colorectal polyps and adenomas. However, the overall mortality, cancer
mortality (SCPS) and lung cancer incidence (ATBC, CARET) was lower in people with
higher baseline β-carotene plasma concentrations in agreement with the results of the
observational studies.
How to explain this failure? With regard to the absence of effect, an easy explanation might
be that β-carotene is the marker of other(s) beneficial compounds found in fruit and
vegetables together with β-carotene. However this is not sufficient to understand the observed
increase in risk. It is worthwhile to underline that this adverse effect occured in subjects at
risk (tobacco use, asbestos exposure, colo-rectal adenomas, etc.). Therefore, β-carotene might
interfere with carcinogenicity at a stage where antioxidant properties might enhance cell
proliferation (Gerber, 1996). β-carotene might act in some situations (high oxygen pressure,
exposure to NO2) as pro-oxidant, capable of damaging DNA or to act on cell signal
transduction at the promotion phase (Carotenoids, IARC, 1998). This would explain the
increase in risk in smokers (ATBC, CARET), and the absence of effects in cohorts with few
smokers (The Physician Health’study and the Women Health’study). Other explanations
include the very high dosage used and the possible necessity to combine several protective
micro-compounds.
Vitamin E significantly lowered the prostate cancer mortality by 41%, and the incidence of
advanced tumors by 40% (Heinonen et al., 1998). It was without effect on latent cancer, and
on the time-lag between diagnosis and death. There was no relationship between prostate
cancer incidence and mortality with vitamin E intake and plasma levels at baseline. Indeed,
this result has to be confirmed but, the results of the studies reported by Eichholzer et al.
(1996) and Gann et al., (1999) are in line with these results although they were only
significant in the smoker groups (Table 25).