world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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PHYTO-ESTROGENS AND<br />
CANCER PEVENTION<br />
Plant foods contain phyto-estrogens, lignans<br />
and isoflavones, which are structurally<br />
similar to the mammalian estrogen,<br />
estradiol-17β. The significance of the<br />
structural similarity of the lignans and<br />
isoflavones to mammalian estrogens and<br />
possible <strong>cancer</strong> preventive effects were<br />
first promulgated in the early 1980s<br />
(Setchell KDR et al., Am J Clin Nutr,<br />
40, 569, 1984; Adlercreutz H, Gastroenterology,<br />
86, 761-6, 1984). The<br />
isoflavones are diphenols and include<br />
daidzein, equol and genistein, all of which<br />
have been shown to bind to α- and especially<br />
β-estrogen receptors (Kuiper GG et<br />
al., Endocrinology, 138, 863-870, 1997).<br />
In common with many other weak estrogens,<br />
the isoflavones have been shown to<br />
be anti-estrogens, competing for estradiol<br />
at the receptor complex, yet failing to<br />
stimulate a full estrogenic response after<br />
binding to the nucleus. In animal models,<br />
inclusion of soy in the feed, a rich source,<br />
reduces mammary tumorigenicity. The<br />
lignans enterolactone and enterodiol are<br />
derived from microbial fermentation of<br />
secoisolariciresinol and matairesinol in<br />
foods, and excreted in urine. These have<br />
to an exposure to estrogens alone (as in<br />
postmenopausal women not using any<br />
exogenous hormones), risk of breast <strong>cancer</strong><br />
is increased further in women who<br />
have elevated plasma and tissue levels of<br />
estrogens in combination with progestogens.<br />
This theory is supported by observations<br />
that postmenopausal women<br />
using estrogen-plus-progestogen preparations<br />
for hormone replacement therapy<br />
have a greater increase in breast <strong>cancer</strong><br />
risk than women using estrogens alone<br />
[10,11]. In premenopausal women, the<br />
estrogen-plus-progestogen theory may<br />
explain why obesity is associated with a<br />
mild reduction in breast <strong>cancer</strong> risk [16],<br />
because obesity may cause chronic<br />
anovulation and decreases in lutealphase<br />
progesterone levels.<br />
78 The causes of <strong>cancer</strong><br />
also been shown to be weakly estrogenic<br />
and anti-estrogenic, and supplements have<br />
been shown to reduce tumorigenesis in a<br />
rodent model of breast <strong>cancer</strong>. However,<br />
proliferative effects of phytoestrogens on<br />
the human breast have also been suggested<br />
(reviewed in Bingham SA et al., Br J Nutr,<br />
79, 393-406, 1998).<br />
The <strong>cancer</strong>s most closely linked to plant<br />
estrogens are the hormone-related carcinomas<br />
of breast and prostate, which<br />
appear to be less common in soy-consuming<br />
populations. However, in the most<br />
recent and largest prospective study of<br />
34,759 women in Hiroshima and Nagasaki,<br />
there was no association between breast<br />
<strong>cancer</strong> risk and soya foods (Key TJ et al., Br<br />
J Cancer, 81, 1248-1256, 1999). Some<br />
recent epidemiological studies include<br />
biomarkers of intake, e.g. urine excretion<br />
of plant estrogens. One recent case-control<br />
study showed that tumour patients excreted<br />
significantly less equol and enterolactone<br />
in 72 hour urine collections than<br />
matched controls, but genistein was not<br />
measured (Ingram D et al., Lancet, 350,<br />
990-992, 1997). A second study showed<br />
that overnight urine total isoflavonoid<br />
excretion, especially of glycetein, was significantly<br />
lower in <strong>cancer</strong> cases compared<br />
Endometrial <strong>cancer</strong><br />
Most observations relating endometrial<br />
<strong>cancer</strong> risk to endogenous and exogenous<br />
sex steroids, as well as to other risk factors<br />
(obesity, ovarian hyperandrogenism<br />
syndromes; see below) are explicable by<br />
the “unopposed estrogen” hypothesis<br />
[13,14]. This stipulates that risk is<br />
increased among women who have high<br />
plasma levels of bioavailable estrogens<br />
and low plasma progesterone, so that the<br />
effect of estrogens is insufficiently counterbalanced<br />
by that of progesterone. The<br />
hypothesis is supported by observations<br />
that proliferation of endometrial cells, a<br />
necessary condition for cells to accumulate<br />
genetic mutations and to expand clonally<br />
with selective growth advantage,<br />
occurs at greater rates during the follicu-<br />
Fig. 2.72 A Nigerian woman boiling milk from<br />
strained soya beans to make soy curd. This is<br />
becoming a substitute for a cheese traditionally<br />
made from more expensive cows’ milk.<br />
with controls (Zheng W et al., Cancer<br />
Epidemiol Biomarkers Prev, 8 35-40,<br />
1999). Messina MJ et al. (Nutr Cancer 21,<br />
113-131, 1994) reviewed the evidence<br />
relating to the impact of soy on <strong>cancer</strong>s<br />
at sites other than the breast.<br />
lar phase of the menstrual cycle (when the<br />
ovary produces estrogens but very little<br />
progesterone), than during the luteal<br />
phase (when the ovaries produce both<br />
estrogens and progesterone). Furthermore,<br />
there are frequent case <strong>report</strong>s of<br />
ovarian hyperandrogenism (polycystic<br />
ovary syndrome) in women developing<br />
endometrial <strong>cancer</strong> before the age of 40<br />
and other studies showing an increased<br />
risk of endometrial <strong>cancer</strong> in polycystic<br />
ovary syndrome patients [13]. Polycystic<br />
ovary syndrome is a relatively frequent<br />
endocrine disorder, with an estimated<br />
prevalence of 4-8%, and in premenopausal<br />
women is associated with frequent anovulatory<br />
menstrual cycles and hence with<br />
impaired luteal-phase progesterone synthesis.<br />
Finally, the theory explains why