Relationship of Nutrition to Cancer Prevention and Treatment

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Relationship of Nutrition to Cancer Prevention
and Treatment

• Arline McDonald, Ph.DDepartment of Preventive
  Medicine
• September 25, 2001

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Proportion of Cancer Deaths Attributable to
Various Factors (Doll and Peto, 1981)
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Worldwide Cancer Data in 2000
U.S.
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Impact of Nutrition on Cancer Mortality

• Treatment
• mitigate dose-limiting complications
• mucositis
• diarrhea
• myalgia, arthralgia
• premature CHD
• peripheral neuropathy
• neurovascular damage
• radiation enteritis
• synergistic effects

• Prevention
• balanced intake of nutrients
• sufficient intake of non-nutrient factors
• appropriate preparation methods
• adequate storage conditions

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Cancer Continuum
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Goals of Cancer Survivors

• Reduce risk of recurrence
• apply preventive approaches
• Rebuild and improve immune system
• insure sufficient intakes of immunosupportive
  micronutrients
• prevent weight loss (energy)
• preserve lean body mass (energy and protein)
• Eliminate debilitating fatigue
• preserve lean body mass (energy and protein)
• adequate intake of iron, copper, magnesium,
  B-vitamins

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Evidence-based relationship established between
diet and cancer
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Epidemiologic Data on Fruit and Vegetable Intake
and Cancer By Site
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Dietary Factors Associated with Reduced Cancer
Risk

• Dietary fiber
• colorectal, pancreas, breast
• Folic acid
• cervix, colorectal
• Vitamin D and calcium
• colorectal, breast
• Antioxidants (nutrient and non-nutrient) from
  foods
• colorectal, lung, breast, cervix, prostate,
  esophagus, stomach

• Vitamin C from foods
• oral cavity, esophagus, lung, stomach, pancreas,
  cervix
• Tea (flavonoids)
• lung, colorectal
• Alpha-tocopherol
• lung
• Soy isoflavones?
• breast

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Dietary Factors Inversely Related to Cancer Risk

• Alcohol
• mouth, pharnyx, larnyx, esophagus,
  liver-convincing
• breast, colon, rectum- probable
• Salt
• stomach- probable
• Sucrose
• colon, rectum

• Meat (especially charbroiled)
• colon and rectum- probable
• Total and Saturated Fat
• lung, colon, rectum, breast, prostate- possible

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Chemopreventive Non-nutritiveDietary Factors
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Role of Dietary Factors in Carcinogenesis
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Inhibitors of Activation

• Inducers of Phase I Biotransformation Enzymes
• cytochrome P450 mono-oxygenase system
• converts hydrophobic to hydrophilic compounds for
  elimination by forming reactive intermediate

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Phase I Activation and Phase II Detoxification
Reactions
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Blocking Agents

• Inducers of Phase II Detoxification Enzymes
• glutathione S-transferases, sulfotransferases,
  UDP-gluronosyltransferases
• phenols, isothiocyanates, flavones, and coumarins
• affect gene expression at transcriptional level
• Binders of free radical intermediates
• antioxidants

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Suppressing Agents

• Inhibit development of cancer subsequent to
  administration of carcinogen
• retinoids and carotenoids
• protease inhibitors
• phenols and polyphenols
• selenium
• Antioxidant protection

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Role of Antioxidants in Carcinogenesis
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Antioxidant Protection
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Other Protective Effects Folic Acid

• Thymidine synthesis inhibited
• lack of methyl donor from methylene-THF4 or
  S-adenosyl-methionine
• DNA hypomethylation
• Uracil misincorporation
• DNA repair by excision
• Increase in fragile sites chromosomal breaks

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Folate Deficiency and DNA Stability
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Other Protective Effects Moderators of Insulin
Sensitivity and Resistance

• Moderators of insulin and insulin-like growth
  factor (IGF-1)
• IGF-1 protects against apoptosis
• insulin and IGF-1 increase aberrant crypt foci
  growth
• precursor of colorectal tumors
• Insulin resistance associated with increased
  tumor promotion in animal models (r0.67)

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Insulin Resistance and Relative Risk of Colon
Cancer
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Other Protective Effects

• Inhibitors of invasive processes
• Stimulate plasminogen activator inhibitors
• reduces plasmin-stimulated degradation of
  extracellular membrane
• dietary fiber, low glycemic index sugars