Prostate cancer and diet

Foods and Cancer

Neal D. Barnard, MDAdjunct Associate Professor of Medicine George Washington University School of Medicine

President, Physicians Committee for Responsible Medicine Washington, DC

Milk and Prostate Cancer

Ganmaa D, Li X, Wang J, Qin L, Wang P, Sato A. Int J Cancer 2002:98,262-267.

Physicians’ Health Study (Harvard)

≥ 2.5 servings/day of dairy products

20,885 physicians

34% increased risk

of prostate cancer

Relative risk: 1.34 (1.04-1.71)Chan JM. Am J Clin Nutr 2001;74:549-54.

Health Professionals Follow-up Study (Harvard)

83% of milk consumed was skim or lowfat

Giovannucci E. Cancer Res 1998;58:442-7.

> 2 servings/day of milk

47,781 health professionals

60% increased risk

of prostate cancer

Relative risk for advanced cancer: 1.6 (95% CI, 1.2-2.1)

Dairy and Prostate Cancer

• > 20 research reports link milk drinking to PC.

• Association with advanced and fatal PC risk

Qin LQ. Nutr Cancer. 2004;48(1):22-27.Gao X. J Natl Cancer Inst. 2005 Dec 7;97(23):1768-1777.Crowe FL. Cancer Epidemiol Biomarkers Prev. 2009;18(5):1333-40Gonzalez CA.. Eur J Cancer. 2010;46(14):2555-62.Butler LM.. Cancer Res. 2010;70(12):4941-8.

Milk Affects Hormones

Milk

↑ IGF-I

↓ Vitamin D

“Insulin-like” = moves sugar into cells

“Growth factor” = encourages cell proliferation

Insulin-Like Growth Factor IInsulin-Like Growth Factor I

Men and women aged 55 to 85 years

Three 8-oz servings of milk for 12 weeks

Serum IGF-I levels: ↑ 10%

P<.001 Heaney RP. J Am Dietetic Asso 1999;99:1228-33.

Milk Drinking Raises Human IGF-IMilk Drinking Raises Human IGF-I

After 10-year follow-up:

cancer patients healthy controls

(n = 152) (n = 152)

IGF-I 269 ng/ml 249 ng/ml

P=0.03

RR = 2.1 (95% CI = 1.3-3.2) per 100 ng/ml IGF-I increment

Chan JM. Science 1998;279:563-6.

Physicians’ Health Study, HarvardPhysicians’ Health Study, Harvard

Vegetarians have lower IGF-I

• Plant-based diet is associated with lower circulating levels of total IGF- I

• EPIC study: 2019 participants– Animal protein, milk, and cheese ↑ IGF-I

– Vegetables, β-carotene ↓ IGF-I

Allen NE. Cancer Epidemiol Biomarkers Prev. 2002;11(11):1441-1448.Norat T. Eur J Clin Nutr. 2007;61(1):91-98.

Vitamin DVitamin D

skin

Vitamin DVitamin D

skin

liver

Vitamin DVitamin D

skin

liverkidney

Vitamin DVitamin D

skin

liverkidney

intestine

Calcium

Vitamin DVitamin D

skin

liverkidney

prostate

intestine

Calcium

Vitamin DVitamin D

skin

liverkidney

prostate

intestine

Calcium

X X

X

Heterocyclic Amines

PhIP Structure*

* 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine)

Processed meats: Bacon Sausage Ham Hot dogs Deli meats

Lycopene vs Prostate Cancer

Health Professionals Follow-Up Study

47,365 participants

≥ 2 tomato sauce servings per weekProstate cancer risk ↓ 23%

Giovannucci E. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 2002;94:391-8.

Vegan Diet and Prostate Cancer

Preventive Medicine Research Institute

84 men with untreated prostate cancer, 1-year study

Control group:

PSA ↑ 6%

6 of the 43 participants required cancer treatment

Vegan group:

PSA ↓4%

No one required treatmentOrnish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174:1065-1069.

Breast Cancer

Association of Dietary Fat & Breast Cancer

USA

SwitzerlandCanada

Denmark

Germany

Norway

New Zealand

FranceUK

SwedenAustralia

ItalyIsrael

Finland

Spain

Poland Hungary

Hong Kong

Yugoslavia

Romania

Japan

0

50

100

150

200

250

600 900 1200 1500

r=0.76

Bre

ast

Can

cer

Inci

den

ce(p

er 1

00,0

00 w

om

en, 4

5-69

yrs

)

Per Capita Fat Availability (kcal)from Prentice, et al. JNCI 1988

Western Diets and Breast Cancer in China

The Shanghai Breast Cancer Study

The “meat-sweet” pattern: meat dessertfish breadcandy milk

30% percent increased breast cancer risk

Cui X. Dietary Patterns and Breast Cancer Risk in the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1443-1448.

Excess body fat

Increasedestrogen activity

Cancer promotion

High-fat / low-fiber dietExcess body fat

Increasedestrogen activity

Cancer promotion

High-fat / low-fiber dietExcess body fat

Increasedestrogen activity

Increased riskof breast cancer

High-fat / low-fiber dietExcess body fat

Increasedestrogen activity

Increased riskof breast cancer

Reduced SHBG

Women’s Health Initiative

48,835 participants, aged 50-79

Diet: 20% fat, ↑ vegetables, fruits, and grains

Fat intake fell from 38% at baseline… to 24% at 1 year, and to 29% at 6 years.

Prentice RI. JAMA. 2006;295:629-642.

Women’s Health Initiative

After 8.1 years:

Overall breast cancer risk ↓9% (not significant).Progesterone-receptor-negative tumor risk ↓24%.

Prentice RI. JAMA. 2006;295:629-642.

Fat Content(Percentage of Calories from Fat)

Leanest beef 29%

Skinless chicken breast 23%

Sea trout 32%

White tuna 16%

Broccoli 8%

Beans 4%

Rice 1–5%

Diet and Breast Cancer Survival

Women’s Intervention Nutrition Study (WINS)

2,437 women with breast cancer

Ages: 48-79, all postmenopausal

Reduced fat (15% of energy) diet vs control

WINSDiet and Cancer Recurrence

All cancers ↓ 24%

Estrogen receptor - ↓ 42%

Estrogen receptor + ↓ 15%

Women’s Healthy Eating and Living Study

3,109 pre- and postmenopausal women previously treated for breast cancer

7 clinical sites, enrollment 1995-2000

Women’s Healthy Eating and Living Study

Comparison diet (“5-a-day”): 5 servings of vegetables and fruits (<30% fat, 20 g fiber)

Intervention diet (“8-a-day”): 5 vegetable servings, 3 fruit servings

16 oz. vegetable juice (15-20% fat, 30 g fiber)

WHEL Study Vegetables-Fruits and Regular Walking

1490 women in comparison group Followed for 5-11 years

Mortality

↑ veg/fruit (7.6 servings) + ↑ activity 4.8%

↓ veg/fruit (3.4 servings) + ↑ activity 10.4%

↑ veg/fruit (7.2 servings) + ↓ activity 10.7%

↓ veg/fruit (3.1 servings) + ↓ activity 11.5%

Pierce JP. J Clin Oncol 2007;25:2345-51.

What about Soy Products?

Source: Wood CE. Biology of Reproduction. 2006;75:477-86.

Soy and Prostate Cancer

Meta-analysis of 15 studies:

Risk for high versus low soy intake:↓26% overall↓48% in Asian populations

Yan L, Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr. 2009;89:1155-1163.

Soy and Breast Cancer

Meta-analysis of 8 studies in Asians and Asian Americans:

High soy intake: 29% ↓ risk of breast cancer.

Wu AH. Br J Cancer. 2004;98:9-14.

Soy and Cancer Recurrence or Mortality in WHEL

<0.0

7

0.07

-1.0

1

1.01

-16.

33

>16.

330

1

P for trend = 0.02

Isoflavone Intake (mg/d)

Haz

ard

Rat

io

Caan BJ. Cancer Epidemiology, Biomarkers, & Prevention. 2011;20:854-8.

Soy and Survival

High soy intake:

54% ↓ risk.

16.3 mg isoflavones = ½ cup soymilk or

2 oz. tofu

Soy and Cancer Recurrence or Mortality

<0.0

7

0.07

-1.0

1

1.01

-16.

33

>16.

330

1

P for trend = 0.02

Isoflavone Intake (mg/d)

Haz

ard

Rat

io

Caan BJ. Cancer Epidemiology, Biomarkers, & Prevention. 2011;20:854-8.

Shanghai Breast Cancer Survival Study

Shu XO. JAMA. 2009;302:2437-43

Soy and Cancer Mortality

<20.

01

20.0

1-36

.50

36.5

1-62

.68

>62.

680

1

Isoflavone Intake (mg/d)

Haz

ard

Rat

io

16.3 mg isoflavones = ½ cup soymilk or 2 oz. tofu

Kaiser Permanente Life After Cancer Epidemiology Study

Guha N. Breast Cancer Research & Treatment. 2009;118:395-405.

Daidzein

0

0.10

-7.7

7

7.78

-149

.59

149.

60-1

,453

.00

1,45

3.10

-9,5

96.5

4

>9,5

96.5

40

1

Daidzein Intake (mcg/d)

Haz

ard

Rat

io

Genistein

0

0.10

-6.9

9

7.00

-220

.61

220.

62-2

,184

.8

2,19

9.82

-13,

025.

87

>13,

025.

870

1

Genistein Intake (mcg/d)

Haz

ard

Rat

io

Glycetein

0-3.

61

3.62

-8.1

6

8.17

-14.

99

15.0

0-78

.53

78.5

4-79

5.39

>796

.39

0

1

Glycetin Intake (mcg/d)

Haz

ard

Rat

io

Soy Intake and Breast Cancer Recurrence

Soy and Breast Cancer Recurrence

<4.0

4.0

- 9.9

910

.0

0.0

0.5

1.0

Isoflavone Intake (mg/d)

Haz

ard

Rat

io

Nechuta SJ. Am J Clin Nutr. 2012;96:123-32.

After Breast Cancer Pooling Project

1. Women’s Healthy Eating & Living Study

2. Shanghai Breast Cancer Survival Study

3. Life After Cancer Epidemiology Study

9,514 breast cancer survivors

Nutrition & Breast Cancer Survival Summary

Reduced body fat → ↑ survival

Reduced dietary fat → ↑ survival

Vegetables & fruits + exercise → ↑ survival

Soy (~2 servings/day) → ↑ survival

Nutrition and Cancer: Mechanisms• Low-fat diets reduce body weight

• Fiber increases hormone elimination

• Low-fat, high-fiber diets boost hormone binding to SHBG

• Isoflavones may reduce risk.

• Avoiding meat reduces carcinogen exposure

PCRM 2009 USDA 2011

Complete Nutrition

Protein

Calcium

Vitamin B12

Acceptability

• No artificial calorie limits.

• No portion sizes.

• No carbohydrate-counting.

• Benefits encourage adherence.

Acceptability Acceptability is similar to that of other therapeutic diets.

• Men and women with heart disease (1992) • Young women with dysmenorrhea (2000) • Postmenopausal overweight women (2004)• Men and women with diabetes (2008)

Barnard ND, Scherwitz L, Ornish D. J Cardiopulmonary Rehab 1992;12:423-31.Barnard ND, Scialli AR, Bertron P, et al. J Nutr Educ 2000;32:314-9. Barnard ND, Scialli AR, Turner-McGrievy GM, et al. J Cardiopulm Rehab 2004;24:229-35.Barnard ND, et al. J Am Diet Assoc 2009;109:263-72.

Body Weight

P-value < 0.0001

Am J Health Promotion, In press

Waist Circumference

Am J Health Promotion, In pressP-value < 0.001

Beginning a Healthful Diet

Step 1. Check out the possibilities

Breakfast

Lunch

Dinner

Snack

Foods to Try

Beginning a Healthful Diet

Step 1. Check out the possibilities

Step 2. Do a 3-week test drive

Optional: Use transition foods

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Resourceswww.pcrm.org