Transcript The Role of Phytoestrogens in Cancer Etiology Susan E. McCann, PhD, RD

The Role of Phytoestrogens
in Cancer Etiology
Susan E. McCann, PhD, RD
Department of Epidemiology
Division of Cancer Prevention and
Population Sciences
Roswell Park Cancer Institute
[email protected]
What are phytoestrogens?
phy·to·es·tro·gen
(plural phy·to·es·tro·gens) noun
Plant sterol: any one of a group of
sterols found in plants that can have
an effect on the body like that of a
hormone. Soybeans and their
products contain phytoestrogens.
Sources of Exogenous
Estrogen Exposure
Dietary Estrogens
Synthetic
Contaminants
Naturally
Occurring
Isoflavonoids
Isoflavones
Lignans
Coumestans
Others
Growth
Xeno
Promoters estrogens
(diethy
(DDT, PCB)
lstilboestrol)
Classification of phytoestrogens
• Isoflavones
– Genistein (plant precursor biochanin A)
– Daidzein (plant precursor formononetin)
• Lignans
– Enterolactone (plant precursor
matairesinol)
– Enterodiol (plant precursor
secoisolariciresinol )
• Coumestans
Food Sources-Isoflavones
• Soybeans
– Soy meal
– Soy grits
– Soy flour
– Tofu, fermented soy products (miso, etc)
– Soy milk
• Lentils
• Dried beans (haricot, broad, kidney, lima)
• Chickpeas
• Processed foods (lunch meats, meal
replacement beverages, donuts)
Food Sources-Lignans
• Flaxseed
• Whole grain cereals (wheat, wheat germ,
barley, hops, rye, rice, brans, oats)
• Fruits, vegetables, seeds (cherries,
apples, pears, stone fruits, sunflower
seeds, carrots, fennel, onion, garlic)
• Beer from hops, bourbon from corn
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Servings per month
30
25
20
15
10
5
0
Food Sources-Coumestans
• Alfalfa sprouts
• Soybean sprouts
18000
16000
14000
12000
10000
8000
6000
4000
2000
0
Daidzein
Enterolactone
Enterodiol
Chemical Structure Estradiol
Chemical structure Isoflavones
Genistein
Daidzein
Matairesinol
Enterolactone
Secoisolari
ciresinol
Enterodiol
Chemical Structure Coumestans
Coumestrol
Potential mechanisms of action
• Competitive inhibition of
endogenous estrogen
• Stimulation of sex hormone
binding globulin synthesis
• Inhibition of angiogenesis and cell
cycle progression
• Additional anticarcinogenic effects:
– Aromatase enzyme inhibition
– Antioxidant properties
Potential mechanisms of action
• At high concentrations, genistein inhibits
proliferation of ER-positive MCF-7 breast
cancer cell lines
• At low concentrations, however,
genistein stimulates proliferation. Also
competes with estradiol for ER binding
and stimulates expression of pS2 mRNA
• Similar stimulatory effects have been
reported for daidzein, equol, and
enterolactone
Animal studies
• Reproductive disturbances in
livestock grazing on clover
• Isoflavone-stimulated uterine
hypertrophy in lab animals
• Decreased breast tumor
proliferation in soy-fed animals
Epidemiologic evidence
• Ecologic
– Populations with high soy food intake
tend to have lower rates of breast,
prostate, and colon cancer
– Migrant populations (presumably
adapting western diet) tend to develop
cancer rates of adopted country
– Specific population subgroups, e.g.,
vegetarians tend to have higher
phytoestrogen intakes and lower
cancer rates
Analytic studies: Phytoestrogens and
hormone sensitive cancers
Study
Study design
Phytoestrogen Cancer
OR
(95% CI)
Urinary genistein Breast 0.83 (0.46-1.51)
Den
Prospective
Urinary enterlactone
1.43 (0.79-2.59)
Tonkelaar
Pietinen Prospective Urinary
enterlactone
Ingram
HornRoss
Strom
Casecontrol
Casecontrol
Breast 0.38 (0.18-0.77)
Breast 0.27 (0.10-0.69)
Urinary equol
Urinary enterlactone
0.36 (0.15-0.86)
FFQ isoflavones
FFQ lignans
Breast
0.92 (0.72-1.2)
1.1 (0.89-1.5)
FFQ daidzein
Prostate 0.57 (0.31-1.05)
Case0.48 (0.25-0.94)
control FFQ coumestrol
Odds ratios and 95% confidence intervals for
risk of breast cancer associated with dietary
lignan intake, Western New York Diet Study
Lignans, mcg/d
Cases
(n)
Controls
(n)
Odds ratio
(95% confidence
interval)
Premenopausal
Low (60-460)
136
Medium (460-670) 98
103
1.00
109
0.70 (0.47-1.03)
High (670-2480)
104
0.49 (0.32-0.75)
67
173
Low (60-460)
Medium (460-670) 139
High (670-2480)
127
Postmenopausal
164
1.00
167
0.75 (0.55-1.04)
163
0.72 (0.51-1.02)
Odds ratios and 95% confidence intervals
for risk of ovarian cancer associated with
dietary lignan intake, WNYDS
Lignans,
mcg/d
Cases
(n)
Controls
(n)
Odds ratio
(95% confidence
interval)
< 304
31
139
1.00
304-408
21
139
0.59 (0.32-1.11)
408-536
30
140
0.81 (0.46-1.46)
536-708
26
139
0.74 (0.41-1.37)
> 708
16
139
0.43 (0.21-0.85)
Odds ratios and 95% confidence intervals for
risk of breast cancer associated with dietary
lignan intake by CYP17 genotype, WNYDS
Lignans,
mcg/d
Cases Controls
(n)
(n)
Odds ratio
(95% confidence
interval)
Premenopausal
A1A2 and A2A2
23
14
1.00
Medium (500-690) 10
High (690-2110)
5
9
15
0.50 (0.14-1.80)
0.12 (0.03-0.50)
19
15
14
0.67 (0.25-1.81)
0.59 (0.20-1.73)
0.71 (0.24-2.08)
Low (130-500)
A1A1
Low (130-500)
23
Medium (500-690) 17
High (690-2110)
18
Odds ratios and 95% confidence intervals for
risk of breast cancer associated with dietary
lignan intake by CYP17 genotype, WNYDS
Lignans, mcg/d Cases Controls
(n)
(n)
A1A2 and A2A2
Low (130-500)
22
Medium (500-690) 20
High (690-2110) 17
A1A1
Low (130-500)
19
Medium (500-690) 14
High (690-2110) 19
Odds ratio
(95% confidence
interval)
Postmenopausal
15
23
1.00
0.58 (0.23-1.48)
17
0.61 (0.22-1.69)
14
15
18
1.05 (0.39-2.87)
0.59 (0.21-1.67)
0.62 (0.23-1.71)
Future directions
• Much of the epidemiologic literature is
supportive of a beneficial effect of
phytoestrogens in cancer prevention
• Biologic mechanisms need to be better
elucidated
• Methods of phytoestrogen
quantification need to be improved
• Genetic susceptibility may play an
important role