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7/30/2019 Woon Puay Koh
1/24
Soy and Reduction of Breast
Cancer Risk among Women in
SingaporeEvidence from the Singapore Chinese Health Study
Woon-Puay Koh
Associate Professor
Department of Epidemiology and Pubic Health
National University of Singapore
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Estrogen and Isoflavones
Estrogen is essential for the growth of breast
cancer
Soy food contains soy isoflavones, which belong
to a class of plant compounds called
phytoestrogen
As naturally occurring selective estrogen
receptor modulators (SERMs), isoflavones canbind to estrogen receptors and inhibit the effects
of endogenous estrogen
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Is soy associated with breast cancer risk?
A meta-analysis of 8 studies done in Asia and among
Asia-Americans with moderate to high intake of soy
showed stepwise reduction of breast cancer risk with
increasing soy intake (Wu et al, Br J Cancer, 2008)
Only one study was prospective in nature while the
rest were case-control studies
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Singapore Chinese Health StudyEligibility criteria: Housing estate residents, ages 45-74 years,
Recruitment period: April 1993 to December 1998
Cohort size: 63,257, with 35,298 women and 27,959 men
Baseline data: In-person interview, focus on smoking, alcohol
intake, physical activity, detailed menstrual and
reproductive history from women, occupational
exposure, etc
Current diet: Validated 165-item food frequency questionnaire
Biospecimen: About 32,000 (50%) gave blood/buccal cells andurine for research
Follow-up: Disease and Death Registries, 2 follow-up
interviews (1999-2004, 2006-2010)
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Measurement of soy intake 7 common soy products, unfermented
8 categories of frequencies from never or hardly ever to 2 or 3 times a day
Color photos of portion sizes
Soy intake expressed in grams of soy protein and equivalent amounts of tofu
per day
Soy isoflavones estimated from summation of genistein, daidzein and glycitein
previously measured in market samples of common soy foods in Singapore
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Soy intake and breast cancer risk
Cases identified via linkage with nationwide
Singapore Cancer Registry
Average follow-up of 6 years, 31 Dec 2005
629 breast cancer cases among 34,028women
Statistical analysis adjusted for age, education,
family history of breast cancer, parity, age atmenarche, body mass index and fat intake
Wu et al, Brit J Cancer, 2008; 99: 196
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Isoflavone
< median
Isoflavone
> median
Number of subjects 17015 17013
Age at recruitment (years) 57.1 (8.2) 55.4 (7.8)
Educational level (%)No formal
Primary
Secondary and higher
43.9
38.0
18.0
36.6
40.0
23.4
BMI (kg/m2) 23.2 (3.3) 23.3 (3.3)
Dietary intake (per day)Mean, SD
Total vegetables (g) 96.2 (53.3) 123.6 (66.6)
Total fruit and juices (g) 170.9 (150.7) 217.1 (169.5)
Seow et al, CEBP, 2009, 18:821
Characteristics of high-soy consumers
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Soy intake N Person-year HR (95% CI)
All subjects
=10.6 mg* 290 170930 0.82 (0.70-0.97)
Soy and breast cancer risk
Premenopausal N Person-year HR (95% CI)
=10.6 mg* 106 52937 1.04 (0.77-1.40)
Postmenopausal
=10.6 mg* 184 117960 0.74 (0.61-0.90)
* isoflavone/1000 kcal/day
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Soy intake All subjects Postmenopausal
0-
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MDM and isoflavone in regulating
breast cancer risk
MDM2 protein
SNP309 (T>G change) of MDM2 gene
p53 protein
Accelerated tumor formation
/ increased cancer risk
TT orGT (low activity) GG (high activity)
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Nested case-control study
403 incident breast cancer cases who gave blood
(64%)
662 controls from a random 3% of the study
population
Genotyping done by the fluorogenic 5-nuclease
assay (TaqMan Assay)
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Postmenopausal women
Cases Controls OR(95% CI)
MDM2
genotype
GG 65 (24.2%) 120 (28.1%) 1.00
GT 150 (56.0%) 212 (49.7%) 1.27 (0.87-1.85)
TT 53 (19.8%) 95 (22.2%) 1.03 (0.65-1.64)
TTor GT(low activity)
203 (75.8%) 307 (71.9%) 1.20 (0.84-1.71)
MDM2 SNP309genotypes in relation
to risk of breast cancer
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All postmenopausal women
Soy isoflavones* Cases Controls OR(95% CI)
=10.6 mg/day 120 220 0.76 (0.56-1.03)
Soy intake in interaction with MDM2 SNP309genotypes in relation to risk of breast cancer
MDM2 SNP309genotype: GT or TT(low activity)
Soy isoflavones* Cases Controls OR(95% CI)
=10.6 mg/day 84 132 0.86 (0.59-1.24)
MDM2 SNP309genotype: GG(high activity)Soy isoflavones* Cases Controls OR(95% CI)
=10.6 mg/day 29 71 0.52 (0.28-0.98)
*isoflavone/1000 kcal/day
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Discussion Significant 18% reduction in breast cancer risk with above
median intake of soy isoflavones (>=10.6 mg/1000kcal/day)
Compatible with results in meta-analysis
Risk reduction was lower and significant
in postmenopausal women
Protective effect of soy was clearest and significant among
women with 10 or more years of follow-up Our findings suggest that soy isoflavones may act via the
down-regulation of the MDM2 oncoprotein as one of its
mechanistic anti-carcinogenic pathways in breast cancer.
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Soy Isoflavones on Risk of ColorectalCancer in the Singapore Chinese
Health StudyEvidence from the Singapore Chinese Health Study
Woon-Puay Koh
Associate Professor
Department of Epidemiology and Pubic Health
National University of Singapore
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Consumption of soy foods in association with colorectal cancer risk in(A) women, with combined risk estimate of 0.79 (95% CI, 0.65-0.97; P = 0.026) and
(B) men, with combined risk estimate: of 1.10 (95% CI, 0.90-1.33; P = 0.358).
Yan L et al. Cancer Epidemiol Biomarkers Prev2010;19:148-1582010 by American Association for Cancer Research
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Meta-analysis showed that soy consumption
was associated with an approximately 21%
reduction in colorectal cancer risk in women.
The protective effect of soy may be due in part
to the potent antioxidant and anti-inflammatory
properties of the bioactive components of soy, or
to the estrogenic effects of soy isoflavones(hormone replacement associated with
decreased colorectal cancer risk in WHI study).
Soy and Colorectal Cancer
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Colorectal Cancer in The SCHS
Colorectal cancer cases identified from the nationwide
Singapore Cancer Registry
1,167 colorectal cases (527 cases in women and 640 cases
in men by 31 Dec 2007)
Mean follow-up time of 11.5 years
Cox proportional hazard model, analysis adjusted for age at
interview, dialect group, interview year, sex (in models with
both men and women), education, body mass index,
cigarette smoking, and intake of alcohol, total calcium, non-
starch polysaccharides and total calories.
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Soy and colorectal cancer risk
Men
Soy intake
g/day
Cases RR (95% CI)*
Q1 (30.9) 194 1.0 (ref)
Q2 (67.8) 145 0.78 (0.62, 0.97)
Q3 (112.0) 147 0.82 (0.65, 1.03)
Q4 (205.5) 154 0.93 (0.71, 1.21)
p for trend 0.7
Women
Cases RR (95% CI)*
141 1.0 (ref)
145 1.15 (0.91, 1.46)
123 1.10 (0.85, 1.42)
118 1.19 (0.88, 1.60)
0.3
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Soy and Bile Acids in Colon Cancer
We reported a dose-dependent, positive association
between saturated fat and colorectal cancer among women
[(RR=1.69; 95% confidence interval=1.08-2.63, p for
trend=0.01), comparing fourth to first quartile] Butler et al Int J
Cancer 2008;124:678.
Dietary saturated fats contribute to colorectal cancer risk, in
part by increasing secondary bile acids in colon
There is convincing experimental evidence that secondary
bile acids can initiate and promoter colorectal cancerdevelopment
Soy protein has bile acid binding property and explains how
soy has been related to the lower enterohepatic circulation,
lower lytic potential and higher fecal excretion of bile acids
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Interaction between fat and soy intakeSaturated fat intake
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Discussion Protective effect of dietary soy against colorectal cancer among
women who consumed within the top 25th percentile of saturatedfats.
First to report a potential modifying effect of saturated fat intake on
the soy-colorectal cancer association.
Bioactive components of soy may protect against colorectal
carcinogenesis by binding to, and thus reducing the lytic activity of
secondary bile acids, which are known colon carcinogens associated
with higher saturated fat intake.
An explanation for why the protective effect of soy isoflavones on
colon cancer risk is most evident among women may be related to
the greater prevalence of estrogen receptor positive colon tumors
among women than men.
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Acknowledgement
Professor Lee Hin Peng
Ms Low Siew Hong
Cohort Study Team
Professor Mimi Yu
Dr Renwei Wang
Supported by Grants from the National Cancer Institute (NIH)
Professor Anna Wu Dr Leslie Butler
http://www.usc.edu/info/welcome/welcome1.htmlhttp://c/Documents%20and%20Settings/cofkwp/Local%20Settings/Temporary%20Internet%20Files/