The%20Role%20of%20Phytoestrogens%20in%20Cancer%20Etiology

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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
• susan.mccann_at_roswellpark.org

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What are phytoestrogens?
phytoestrogen
(plural phytoestrogens)
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.
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Sources of Exogenous Estrogen Exposure
Dietary Estrogens
Synthetic Contaminants
Naturally Occurring
Growth Promoters
Xeno estrogens
Lignans
Others
Isoflavonoids
(diethy lstilboestrol)
Coumestans
Isoflavones
(DDT, PCB)
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Classification of phytoestrogens

• Isoflavones
• Genistein (plant precursor biochanin A)
• Daidzein (plant precursor formononetin)
• Lignans
• Enterolactone (plant precursor matairesinol)
• Enterodiol (plant precursor secoisolariciresinol
  )
• Coumestans

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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)

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(No Transcript)
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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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Top ten contributors to lignan intake, Western
New York Health Study (1996-2001)
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Food Sources-Coumestans

• Alfalfa sprouts
• Soybean sprouts

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Mean urinary excretion of phytoestrogens among
different populations
18000
16000
14000
12000
10000
8000
6000
4000
2000
0
Daidzein
Japanese Women
Finnish Omnivores
Finnish Vegetarians
Enterolactone
Oriental Immigrants
American Omnivores
Finnish Breast Cancer
American Vegetarians
American Macrobiotics
Enterodiol
Adapted from Adlercreutz Baillieres Clinical
Endocrinology and Metabolism 199812(4)605-623
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Chemical Structure Estradiol
Chemical Structure Estradiol
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Chemical structure Isoflavones
Genistein
Daidzein
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Chemical Structure-Lignans
Enterolactone
Matairesinol
Secoisolariciresinol
Enterodiol
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Chemical Structure Coumestans
Coumestrol
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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

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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

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Animal studies

• Reproductive disturbances in livestock grazing on
  clover
• Isoflavone-stimulated uterine hypertrophy in lab
  animals
• Decreased breast tumor proliferation in soy-fed
  animals

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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

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Analytic studies Phytoestrogens and hormone
sensitive cancers
Cancer
Phytoestrogen
OR (95 CI)
Study design
Study
Urinary genistein Urinary enterlactone
Den Tonkelaar
Breast
0.83 (0.46-1.51) 1.43 (0.79-2.59)
Prospective
Urinary enterlactone
Pietinen
Breast
0.38 (0.18-0.77)
Prospective
Breast
0.27 (0.10-0.69) 0.36 (0.15-0.86)
Urinary equol Urinary enterlactone
Case-control
Ingram
Horn-Ross
Case-control
Breast
FFQ isoflavones FFQ lignans
0.92 (0.72-1.2) 1.1 (0.89-1.5)
FFQ daidzein FFQ coumestrol
0.57 (0.31-1.05) 0.48 (0.25-0.94)
Prostate
Case-control
Strom
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Odds ratios and 95 confidence intervals for risk
of breast cancer associated with dietary lignan
intake, Western New York Diet Study
Odds ratio (95 confidence interval)
Controls (n)
Cases (n)
Lignans, mcg/d
Premenopausal
1.00
103
136
Low (60-460)
Medium (460-670)
0.70 (0.47-1.03)
109
98
0.49 (0.32-0.75)
104
67
High (670-2480)
Postmenopausal
1.00
164
173
Low (60-460)
Medium (460-670)
0.75 (0.55-1.04)
167
139
High (670-2480)
0.72 (0.51-1.02)
163
127
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Odds ratios and 95 confidence intervals for risk
of ovarian cancer associated with dietary lignan
intake, WNYDS
Lignans, mcg/d
Odds ratio (95 confidence interval)
Cases (n)
Controls (n)
1.00
139
31
lt 304
0.59 (0.32-1.11)
139
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304-408
0.81 (0.46-1.46)
140
30
408-536
0.74 (0.41-1.37)
139
26
536-708
0.43 (0.21-0.85)
139
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gt 708
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Odds ratios and 95 confidence intervals for risk
of breast cancer associated with dietary lignan
intake by CYP17 genotype, WNYDS
Lignans, mcg/d
Odds ratio (95 confidence interval)
Controls (n)
Cases (n)
Premenopausal
A1A2 and A2A2
1.00
14
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Low (130-500)
0.50 (0.14-1.80)
9
10
Medium (500-690)
0.12 (0.03-0.50)
15
5
High (690-2110)
A1A1
0.67 (0.25-1.81)
19
23
Low (130-500)
Medium (500-690)
0.59 (0.20-1.73)
15
17
0.71 (0.24-2.08)
14
18
High (690-2110)
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Odds ratios and 95 confidence intervals for risk
of breast cancer associated with dietary lignan
intake by CYP17 genotype, WNYDS
Lignans, mcg/d
Odds ratio (95 confidence interval)
Controls (n)
Cases (n)
Postmenopausal
A1A2 and A2A2
1.00
15
22
Low (130-500)
0.58 (0.23-1.48)
23
20
Medium (500-690)
0.61 (0.22-1.69)
17
17
High (690-2110)
A1A1
1.05 (0.39-2.87)
14
19
Low (130-500)
0.59 (0.21-1.67)
15
14
Medium (500-690)
18
19
High (690-2110)
0.62 (0.23-1.71)
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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