FROM:
Cancer Res 1999 (Mar 15); 59 (6): 1225–1230
Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM,
Hennekens CH, Stampfer MJ
Department of Preventive Medicine,
Northwestern University Medical School,
Chicago, Illinois 60611, USA.
pgann@nwu.edu
Dietary consumption of the carotenoid lycopene (mostly from
tomato products) has been associated with a lower risk of
prostate cancer. Evidence relating other carotenoids,
tocopherols, and retinol to prostate cancer risk has been
equivocal. This prospective study was designed to examine the
relationship between plasma concentrations of several major
antioxidants and risk of prostate cancer. We conducted a nested
case-control study using plasma samples obtained in 1982 from
healthy men enrolled in the Physicians' Health Study, a
randomized, placebo-controlled trial of aspirin and beta-
carotene.
Subjects included 578 men who developed prostate cancer within 13
years of follow-up and 1294 age- and smoking status-matched
controls. We quantified the five major plasma carotenoid peaks
(alpha- and beta-carotene, beta-cryptoxanthin, lutein, and
lycopene) plus alpha- and gamma-tocopherol and retinol
using high-performance liquid chromatography.
Results for plasma beta-carotene are reported separately. Odds
ratios (ORs), 95%
confidence intervals (CIs), and Ps for trend were calculated for
each quintile of plasma antioxidant using logistic regression
models that allowed for adjustment of potential confounders and
estimation of effect modification by assignment to either active
beta-carotene or placebo in the trial. Lycopene was the only
antioxidant found at significantly lower mean levels in cases
than in matched controls (P = 0.04 for all cases). The ORs for
all prostate cancers declined slightly with increasing quintile
of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06;
P, trend = 0.12); there was a stronger inverse association for
aggressive prostate cancers (5th quintile OR = 0.56, 95% CI =
0.34-0.91; P, trend = 0.05).
In the placebo group, plasma lycopene was very strongly related
to lower prostate cancer risk (5th quintile OR = 0.40; P, trend
0.006 for aggressive cancer), whereas there was no evidence for a
trend among those assigned to
beta-carotene supplements. However, in the beta-carotene group,
prostate cancer risk was reduced in each lycopene quintile
relative to men with low lycopene and placebo.
The only other notable association was a reduced risk of
aggressive cancer with higher alpha-tocopherol levels that was
not statistically significant. None of the associations for
lycopene were confounded by age, smoking, body mass index,
exercise, alcohol, multivitamin use, or plasma total cholesterol
level.
These results concur with a recent prospective dietary analysis,
which identified lycopene as the carotenoid with the clearest
inverse relation to the development of prostate cancer. The
inverse association was particularly apparent for aggressive
cancer and for men not consuming beta-carotene supplements. For
men with low lycopene, beta-carotene supplements were associated
with risk reductions comparable to those observed with high
lycopene.
These data provide further evidence that increased consumption of
tomato products and other lycopene-containing foods might reduce
the occurrence or progression of prostate cancer.