Nutrition in Cancer Prevention and Treatment

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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 …

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

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  • 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 1
  • 2. Learning Objectives 1. 2. 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 Nutrition @ DEAKIN 2
  • 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) Nutrition @ DEAKIN 3
  • 4. Cancer in Australia: 2007 Cancer in Australia 2010: an overview. Cancer Series no. 60 AIHW. www.aihw.gov.au/publication-detail/?id=6442472454 Nutrition @ DEAKIN 4
  • 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 Nutrition @ DEAKIN 5
  • 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 Nutrition @ DEAKIN 6
  • 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 Nutrition @ DEAKIN 7
  • 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 Nutrition @ DEAKIN 8
  • 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) Nutrition @ DEAKIN 9
  • 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 Nutrition @ DEAKIN 10
  • 11. Dietary Modification of BC Risk • • • • • • • • 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 Nutrition @ DEAKIN 11
  • 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) Nutrition @ DEAKIN 12
  • 13. Does Red Meat Cause Cancer? • • • ↑ 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 Nutrition @ DEAKIN 13
  • 14. Antioxidants and Cancer Prevention • Free radicals can damage DNA • Antioxidants can neutralise the free radicals, preventing • • 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? Nutrition @ DEAKIN 14
  • 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 Nutrition @ DEAKIN 15
  • 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 Nutrition @ DEAKIN 16
  • 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 Nutrition @ DEAKIN 17
  • 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 Nutrition @ DEAKIN 18
  • 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 Nutrition @ DEAKIN 19
  • 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 Nutrition @ DEAKIN 20
  • 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 Nutrition @ DEAKIN 21
  • 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 Nutrition @ DEAKIN 22
  • 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 Nutrition @ DEAKIN 23
  • 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 Nutrition @ DEAKIN 24
  • 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 Nutrition @ DEAKIN 25
  • 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 Nutrition @ DEAKIN 26
  • 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) Nutrition @ DEAKIN 27
  • 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 Nutrition @ DEAKIN 28
  • 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 Nutrition @ DEAKIN 29
  • 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 Nutrition @ DEAKIN 30
  • 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 Nutrition @ DEAKIN 31
  • 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 Nutrition @ DEAKIN 32
  • 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 Nutrition @ DEAKIN 33
  • 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 Nutrition @ DEAKIN 34
  • 35. Recommendations for Cancer Prevention The Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective www.dietandcancerreport.org 1. 2. 3. 4. 5. 6. 7. 8. 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 Nutrition @ DEAKIN 35
  • 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 Nutrition @ DEAKIN 36