This presentation will help you to understand the influence that dietary and lifestyle factors play in the prevention and causation of cancer. It outlines the important nutritional considerations for patients undergoing treatment for cancer and reviews procedures to improve patient safety by knowing the risks and benefits of antioxidant supplementation during cancer treatment

1. Nutrition in Cancer Prevention and
Treatment
Associate Professor Tim Crowe
School of Exercise and Nutrition Sciences
Deakin University
tim.crowe@deakin.edu.au
@CroweTim
www.thinkingnutrition.com.au
Nutrition @ DEAKIN
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2. Learning Objectives
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3.
To understand the influence that dietary and
lifestyle factors play in the prevention and
causation of cancer
To be aware of the important nutritional
considerations for patients undergoing
treatment for cancer
Review procedures to improve patient safety by
knowing the risks and benefits of antioxidant
supplementation during cancer treatment
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3. Cancer in Australia
Summary
• Cancer accounts for ~30% of all deaths
• 108,368 new cancers diagnosed in 2007
(excluding non-melanocyte skin cancers)
• 39,884 deaths in 2007 from cancer
In order of incidence: Prostate, colorectal,
breast, melanoma and lung (61% of all cases)
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4. Cancer in Australia: 2007
Cancer in Australia 2010: an overview. Cancer Series no. 60 AIHW.
www.aihw.gov.au/publication-detail/?id=6442472454
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5. Trends in Incidence and Mortality
In Australia between 1982-2007
• 27% ↑ incidence (age standardised)
• Rise in incidence of most cancers
• 16% ↓ mortality (age standardised)
• Falls in mortality for most cancers except liver,
melanoma, and lung cancer (in women)
Cancer in Australia 2010: an overview. Cancer Series no. 60 AIHW.
www.aihw.gov.au/publication-detail/?id=6442472454
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6. Lifestyle Factors Contributing to
Cancer Risk
Fraction of cancer attributable to lifestyle and
environmental factors in the UK in 2010
Parkin DM and Walker LC. Br J Cancer 2011;105:577-581
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7. Lifestyle Factors Associated with
Reduced Cancer Risk
Dietary Factor
Cancer
Fibre
Colorectal*, oesophagus,
Fruits and Vegetables
Oral cavity, oesophagus, lung, stomach, colorectal
Physical Activity
Colorectal*, breast, oesophagus, pancreas, liver,
endometrial
Lactation
Breast*
Calcium
Colorectal
Dairy foods
Colorectal
Fish
Colorectal
Garlic
Colorectal
Selenium
Lung, colorectal, prostate
Folate
Oesophagus, pancreas, colorectal
*Cancers
bolded are where evidence is the strongest
The Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of
Cancer: a Global Perspective www.dietandcancerreport.org
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8. Lifestyle Factors Associated with
Increased Cancer Risk
Dietary Factor
Cancer
Overweight and obesity
Oesophagus, pancreas, colorectal, breast (postmenopausal), endometrial, kidney
Alcohol
Oral cavity, oesophagus, liver, colorectal, breast
Salted foods
Stomach, nasopharynx
Red meat
Colorectal
Aflatoxin
Liver
Grilled/BBQ foods
Colorectal, stomach
Very hot foods and drinks
Oral cavity, oesophagus
*Cancers
bolded are where evidence is the strongest
The Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of
Cancer: a Global Perspective www.dietandcancerreport.org
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9. Obesity and Cancer
• Cancers most likely: breast,
•
colorectal, kidney, endometrium,
oesophagus and pancreas
True incidence likely
underestimated due to effect
of smoking and self-reported
height and weight in some studies
(↑BMI = ↑under-reporting)
Mechanism?
• ↑ Insulin, insulin growth factor-1 and/or sex steroids
• Reflux (for oesophageal cancer)
• Chronic inflammation (↑ oxidative stress)
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10. Breast Cancer
• Life-time risk in the
•
•
•
western world is 10%
and associated with a
western lifestyle
Risk increases with age
Genetics (family history)
explain 10% of cases
Hormonal and
dietary/lifestyle factors
play the biggest role
www.sogc.org/media/guidelines-oc_e.asp
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11. Dietary Modification of BC Risk
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Increased dietary fibre ↓ estrogen
Levels of estrogen are lower in
vegetarians
Dietary restriction shown to lower
IGF-1, increase SHBG, lower insulin
Weight loss
Alcohol: ↑ estrogen concentration, ↓ folate, direct effects on
breast tissue
Omega-3s may be protective: ?anti-proliferative effect
Reduced fat diets shown to ↓ circulating estrogen
? Phytoestrogens (soy products) protective
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12. Dietary Fibre and Colorectal Cancer
• Dietary fibre (and resistant starch), especially from
•
•
cereal and pulses, is likely protective
Unclear if it is the fibre or other nutrients in the
food
Range of physiological actions:
–
–
–
–
pH
Bulking effect
Butyric acid (anti-proliferative)
Transit time (also affected by exercise)
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13. Does Red Meat Cause Cancer?
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↑ risk estimates in the range of 20 to 50% for highest vs
lowest intakes of red meat in prospective studies
Not clear if it’s the intake of red meat (?excess Fe), form of
meat (esp. processed), or the way meat is cooked
Nitrosamines (endogenous and from nitrate preservatives)
•
Cooking (charring) of meat produces two types of carcinogens
– Polycyclic aromatic hydrocarbons (PAHs)
– Heterocyclic amines (HCAs)
•
World Cancer Research Fund 2007 report* rates
the evidence as ‘Convincing’
*The
Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: a
Global Perspective www.dietandcancerreport.org
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14. Antioxidants and Cancer Prevention
• Free radicals can damage DNA
• Antioxidants can neutralise the free radicals, preventing
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•
the cancer initiation process
Additional benefits may lie in inhibiting proliferation and
angiogenesis
Observational epidemiological studies and case-control
studies strongly supported the theory
What do RCTs tell us?
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15. ATBC Study
Premise: high fruit and vegetable intake protective against
lung cancer and smokers have lower serum retinol
concentrations
• 29,133 male smokers in Finland, 50-69 y.o.
• Given either Vit E (50 mg), beta-carotene (20 mg), both,
or placebo daily for 5-8 years
Results: 18% more lung cancers and 8% higher mortality
with beta-carotene (effect only seen in drinkers)
32% decrease in incidence of prostate cancer in group
taking vitamin E
ATBC. New Engl J Med 1994:330:1029-35
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16. CARET Study
• 14,000 smokers and ex-smokers 50-69 y.o.
• Beta-carotene (30 mg) and retinol (25,000 IU) for 4
yrs
28% more cancer and 17% greater mortality
CARET. New Eng J Med 1996;334:1150-5
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17. ATBC and CARET Follow Up
8 yrs after the end of ATBC
• Intervention effect of beta-carotene disappeared
and no ‘late’ preventative effects seen
• Effect of vitamin E on prostate cancer reduced
5 yrs after the end of CARET
• Elevated risk post-trial seen in females
ATBC Follow-up JAMA 2003;290:476-85
CARET Follow-up J Nat Cancer Inst 2004;96:1743-50
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18. Beta-Carotene and Non-smokers?
• Physicians’ Health Study (22,000 males, 11%
smokers)
– Beta-carotene not harmful after 12 yrs
• 44% lower risk of adenoma recurrence in
non-smokers and drinkers, but double the
risk in smokers and drinkers
Baron et al. J Nat Cancer Inst 2003;95:717-22
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19. Mechanisms?
1. Beta-carotene: pro-oxidant activity at high O2
pressure in lungs
2. Smoking increases production of oxidised betacarotene metabolites
3. High beta-carotene concentrations may
decrease tissue retinoic acid
4. Vitamin E: displacement of other fat soluble
vitamins
5. Synergistic effect important
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20. HOPE-TOO, WHS and WACS
HOPE-TOO: 5,900 patients randomised to 400 IU Vit E/day for
7.1 yrs
• No differences in cancer incidence and deaths or major
CVD events (↑ in HF)
WHS: 40,000 women (> 45 y.o.), RCT of 600 IU Vit E/day or
placebo for 10 yrs
• No reduction in cancer or CVD events
WACS: 8,100 women, 600 IU Vit E, 500 mg Vit C, 50 mg betacarotene or placebo for 9.4 yrs
• No reduction in cancer morbidity of mortality
• Indication of ↑ pancreatic and lung cancer with Vit C
HOPE-TOO JAMA 2005;293:1338-47 WACS J Nat Cancer Inst 2009;101:14-23
WHS JAMA 2005;294:56-65
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21. Se, Vitamin E and Prostate Cancer
Secondary results from earlier studies showed ↓ prostate
cancer with Se and vitamin E supplements. Larger dedicated
RCTs now done
SELECT: RCT (double blind) of 35,500 men > 50 yrs allocated to
Se (200 μg/d), vitamin E (400 IU/d), Se + E, or placebo on
prostate cancer occurrence Lippman et al. JAMA 2009;301:39-51
• Median follow up of 5.5 yrs: no reduction in prostate cancer
or any other major cancers
• Trial stoped early because of evidence of harm (nonsignificant ↑ T2DM with Se and ↑ prostate cancer with
vitamin E)
• Further follow up confirmed 17% ↑ prostate cancer
with vitamin E Klein et al. JAMA 2011;306:1549-1556
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22. Se, Vitamin C and Prostate Cancer
Physicians Health Study II
• 14,600 male US physicians randomised to vitamin E
(400 IU/2d), vitamin C (500 mg/d), E + C, or placebo
• Mean follow up of 8 yrs: no reduction in prostate
cancer or any other major cancers with any
combination of supplements
PHSII JAMA 2009;301:52-62
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23. SU.VI.MAX Study
• RCT with 7 yr follow up using low-dose
supplements
• 13,017 French adults (35-60 y.o.)
• Single daily capsule:
• 120 mg vitamin C
• 30 mg vitamin E
• 6 mg beta-carotene
• 100 µg Se
• 20 mg Zn
Hercberg S et al. Arch Int Med 2004;164:2335-42
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24. SU.VI.MAX Results
• No change in total cancer or CVD incidence vs placebo
• No change in all-cause mortality
• In men: 31% lower incidence of cancer and 37%
reduction in all-cause mortality
• ? Benefit because of lower baseline antioxidant status
(vitamin C and beta-carotene) in men
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25. Effect of Antioxidant Supplements versus Placebo or
no Intervention on Cancer Incidence in 22 RCTs
Myung S et al. Ann Oncol 2010;21:166-179
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26. Diet: Treatment and Recovery
• Studies on diet post treatment few in number
and almost all observational
• Some evidence that ‘prudent’ diet high in F&V,
wholegrains, legumes, fish and low in fat lowers
breast and colorectal Ca recurrence and
mortality*
• Due to improved survival rates, healthy diet
important because patients may die from other
diseases related to diet
*Robein K et al. J Am Diet Assoc 2011;111:368-375
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27. Anticancer Therapies
• RTx → ROS (reactive oxygen
species) production
• CTx → several modes of action
– Many rely on ROS production:
• Anthracyclines (e.g. doxorubicin)
• Alkylating agent (e.g. cyclophosphamide, ifosfamide)
• Platinum complexes (e.g. cisplatin, carboplatin)
• Cytotoxic antibiotics (e.g. bleomycin, mitomycin-C)
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28. Antioxidants during Treatment
Estimates of 13-87% of Ca patients use antioxidant supplements
For
• May protect normal cells from ROS damage, allowing better
tolerance of treatment and higher dosage
• Enhance cytotoxic CTx by blocking ROS (which can slow rapid
cell proliferation by prolonging G1 phase)
Against
• Quenching ROS reduces efficacy
• May repair damage to cancer cells caused by ROS damage
from treatment and inhibit apoptosis
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29. Antioxidants during Treatment
Folate, methotrexate and 5-FU
• Patients with higher folate intake may experience
less treatment-related side effects
• Folate proposed to be protective against Ca
development (DNA mutation and replication repair),
but cell-growth promoting once Ca developed
• Concern that may interfere with methotrexate
therapy efficacy and promote tumour growth*
• Vitamin C shows reduced cytotoxic effect in vitro
*Robien
K. Nutr Clin Prac 2005;20:411-22
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30. Antioxidants and RTx: a RCT
• 540 patients, stage I or II H&N Ca
• RCT (double blind) with vitamin E (400 IU/day)
and beta-carotene (30 mg/day) on first day of
RTx and then for 3 yrs post
• Beta-carotene ceased after first 156 patients
enrolled
What happened?
Bairati I et al. J Clin Oncol 2005;23:5805-13
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31. Follow-up: Adverse Events
After median follow-up of 52 months:
• Those in supplement arm tended to have less
side-effects (OR=0.72; CI=0.52-1.02)
• When combined with beta-carotene, ↓ side
effects seen (OR=0.38; CI=0.20-0.74)
• QOL not improved
• Local recurrence tended to be higher
(HR=1.37; CI=0.93-2.02)
Bairati I et al. J Clin Oncol 2005;23:5805-13
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32. Follow-up: Cancer Recurrence
After median follow-up of 52 months:
• Higher rate of second primary cancer incidence in
supplement group (HR=2.88; CI=1.56-5.31)
• Higher rate of recurrence or second primary cancer
in supplement group (HR=1.86; CI=1.27-2.72)
• Higher all-cause mortality (HR=1.38; CI=1.03-1.85)
• Lower rate of recurrence or second primary cancers
after supplementation finished, though not
statistically significant
Bairati I et al. J Clin Oncol 2005;23:5805-13
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33. Commentary on Antioxidants
Review of 9 studies for RTx (3 RCTs, 2 metaanalyses) and 16 RCTs for CTx*
“On the basis of our review of the published randomized clinical trials, we
conclude that the use of supplemental antioxidants during chemotherapy
and radiation therapy should be discouraged because of the possibility of
tumor protection and reduced survival.”
"Despite some intriguing studies that have suggested the benefit of
adjunctive antioxidant treatments in cancer patients, the totality of the
available evidence is equivocal at best and leaves us with serious
concerns about the potential for harm.”
*Lawenda
B et al. J Natl Cancer Inst 2008;100:773-783
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34. Indications for Supplements in Ca Treatment
• During and after treatment, probable benefit
to taking multivitamin at 100% of RDI
Also when:
• Biochemically demonstrated deficiency
• Chronic poor nutrient intake
• To meet public health recommendations
• Known health problems related to Ca
treatment
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35. Recommendations for Cancer Prevention
The Second Expert Report, Food, Nutrition, Physical Activity, and the
Prevention of Cancer: a Global Perspective www.dietandcancerreport.org
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Be as lean as possible within the normal range of body weight
Be physically active as part of everyday life
Limit consumption of energy-dense foods. Avoid sugary drinks
Eat mostly foods of plant origin
Limit intake of red meat and avoid processed meat
Limit alcoholic drinks
Limit consumption of salt. Avoid mouldy grains or legumes
Aim to meet nutritional needs through diet alone rather than
supplements
9. Mothers to breastfeed; children to be breastfed
10. For cancer survivors: follow the recommendations for
cancer prevention
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36. Nutrition and Physical Activity
Recommendations
American Cancer Society Guidelines on nutrition and physical
activity for cancer prevention: reducing the risk of cancer
with healthy food choices and physical activity
CA: A Cancer Journal for Clinicians 2006;56:254-81
Nutrition and physical activity during and after cancer
treatment: An American Cancer Society guide for informed
choices
CA: A Cancer Journal for Clinicians 2006;56:323-53
Available free online from:
http://caonline.amcancersoc.org
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