woon puay koh

7/30/2019 Woon Puay Koh

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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
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