Nutrition and Cancer Flashcards
Carcinogenesis Pathways
-
Genetic
- oncogenes, proto-oncogenes, tumor suppressor genes
-
Biologic
- transforming viruses
-
Physical
- radiation, UV → DNA damage
-
Chemical carcinogens
- procarcinogens → activation → DNA damage
- inflammation → free radicals → DNA damage
- excess growth hormone → cancer progression
Alcohol
Associated Cancers
-
Known increased risk:
- mouth
- larynx
- pharynx
- esophagus
- liver
-
Observed increased risk:
- breast
- colon
Alcohol
Cancer Mechanism
-
Excess acetaldehyde
- EtOH → acetaldehyde by alcohol dehydrogenase in liver
- Acetaldehyde → Krebs cycle ⟾ energy
- Excess acetaldehyde → systemic ⟾ impaired mitochondrial function & cirrhosis
-
Excess NADH
- ⊕ pyruvate → lactic acid ⟾ ⊖ gluconeogenesis ⟾ acidosis & hypoglycemia
- ⊕ lipogenesis ⟾ obesity
- ⊕ ETC in mitochondria & ⊖ lipid metabolism ⟾ ⊖ Krebs cycle & acetyl CoA accumulation ⟾ hyperlipidemia and ketosis
- Induces hepatic Phase I enzymes (cyto-P450 enzymes) ⟾ hydroxylation/oxidation ⟾ activation of compounds
Obesity Associated Cancers
Clear Increased Risk
-
Clear increased risk:
- post-menopausal breast cancer
- endometrial (uterine) cancer
- colon ca
- esophageal ca
- kidney ca
Obesity Associated Cancers
Observed Increased Risk
-
Observed increased risk:
- pancreas
- gallbladder
- thyroid
- ovary
- cervix
- prostate
Obesity
Cancer Mechanism
-
Breast & endometrial ca
- peripheral fat hormone production ⟾ ↑ estrogen
-
Colon ca
- associated with IGF-1/insulin
-
Esophageal & gastric ca
- increased reflux ⟾ Barrett’s esophagus
- Kidney ⟾ unknown
Meat
Associated Cancers
-
Epidemiological studies
- colon
- pancreatic
- prostate
-
Animal studies
- breast
- colon
- liver
- skin
Meat
Carcinogenic Compounds
-
Nitrates/nitrites
- preservatives in processed meats
- binds proteins to form nitrosamines
- vit C inhibits reaction
-
Byproducts of combustion
-
polycyclic aromatic hydrocarbons
- generated by combustion of fat in high heat (grilling)
- from coal tar and auto exhaust
-
heterocyclic amines
- amino acids + creatine combine in heat
-
polycyclic aromatic hydrocarbons
Meat
Cancer Mechanism
Benzopyrene (a polycyclic aromatic hydrocarbon) activated by Phase I enzymes ⟾ becomes carginogenic.
Active benzopyrene diol epoxide intercalates into DNA ⟾ replication errors.
p53 tumor suppressor gene possible target.
Aflatoxin
- Produced by aspergilus species (mold)
- high heat and humidity
- infects before or after harvest
- areas of endemic soil contamination
-
Found in:
- corn, cereals, wheat, rice
- peanuts and sunflower seeds
- spices including pepper and ginger
- nuts
- Hepatocellular cancer higher in Aspergillus flavus endemic areas.
Aflatoxin
Cancer Mechanism
Hepatic Aflatoxin B1 metabolism ⟾ ROS.
Epoxide binds DNA ⟾ DNA adducts.
p53 is a target.
Benefits
of
Vegetables
-
Sources of vitamins and minerals:
-
Vit A
- retinoic acid is a differentiation agent
-
Folate
- reduces cancer risk
-
Vit A
-
Dietary Fiber
-
Binds carcinogens
- Shortens transit time
- Increases bulk
-
Recommmended intake
- 25 g for women
- 38 g for men
-
Binds carcinogens
-
Induction of Phase II Enzymes
-
Conjugation of carcinogens
- with glutathione, glucuronidation, sulfation
- Isothiocyanates or organosulfur molecules
- Broccoli, cauliflower, cabbage, radishes, garlic, onion
-
Conjugation of carcinogens
Benefits
of
Fruits
Source of:
- Vitamins
-
Monoterpenes
-
reduces farnesylation of G-protein receptors
- may decrease growth factor-mediated proliferation of cancer cells
-
reduces farnesylation of G-protein receptors
Vitamin Supplementation
-
Tocopherols (Vit E) and carotenoids (Vit A)
- membrane-associated antioxidants
-
Vit C
- serum/ECF associated antioxidant
- recharges tocopherol back to antioxidant state
-
Selenium
- needed for glutathione peroxidase
-
Manganese
- used by antioxidants
-
Iron
- used by superoxide dismutase
American Cancer Society
Nutrition & Physicial Activity Guidelines
-
Maintain a healthy weight
- balance activity and intake
- avoid excess gain
- achieve healthy weight if overweight
-
Adopt a physically active lifestyle
- 30 mins of moderate activity 5 days a week
-
Consume a healthy diet with emphasis on plant sources
- portion control
- 5 servings of variety of fruits and vegetables
- whole grains
- limit processed and red meats
-
Limit alcohol consumption
- 1 drink for women, 2 for men
Cancer Cachexia
Causes
May be due to:
- Depression
- Decreased PO intake
- Increased BEE due to IL-1, IL-6, and TNF-𝛼
- Preferential muscle catabolism
Surgical and Radiation Therapy
Considerations
- Perioperative NPO status
-
Head, neck, and esophagus ca
- dysphagia, odynophagia
- xerostomia (dry mouth)
- ageusia, dysgeusia (lost/impaired taste sensation)
-
GI/GYN/GU ca
-
early satiety
- tumor compression or surgical restriction
-
partial/complete obstruction
- adhesions or tumors
-
early satiety
-
Hepatic/pancreatic ca
- impaired digestion/absorption
Cytotoxic Chemotherapy
Considerations
- Nausea/vomiting
- Anorexia
- Taste alterations
-
Cytotoxic effects:
-
intestinal lining
- enteritis, colitis, typhlitis, perforation
-
hair and nails
- cosmetic, depressing
-
neuropathy
- pain and reduced sensation
-
nephropathy
- acute/chronic renal insufficiency
-
hepatotoxicity
- reduced ability to detoxify
- increased fatty replacement
- reduced synthetic function
-
intestinal lining
Other Chemotherapy
Considerations
-
Steroids
- immunosuppression
- centripetal obesity
- muscle wasting
- insulin resistance
-
Anti-estrogen therapy
- weight gain
-
Anti-androgen therapy
- muscle wasting
Herceptin
Molecular Target Drugs
Effects
cardiomyopathy
Erbitux
Molecular Target Drugs
Effects
skin toxicity
Gleevec
Molecular Target Drugs
Effects
colitis
Sorafenib
Molecular Target Drugs
Effects
muscle wasting
Bevacizumab
Molecular Target Drugs
Effects
muscle wasting
Nutritional Interventions
How to combat cachexia:
-
Increase PO intake / dietary supplements
- no efficacy
-
Increase appetite
- progestational agents
- medroxyprogesterone
- cannabinoids ⟾ better in HIV
- progestational agents
-
Combat catabolism
- androgens ⟾ not effective
-
Block TNF
- 3 randomized controlled trails ⟾ negative
Enteral Nutrition
Tube Feeding
-
Nasogastric tube
- short-term solution
- least invasive
- aspiration risk
- not an option for upper GI surgeries
-
Gastrostomy tube
- minimally invasive
- aspiration risk
- long lasting
- not an option for upper GI surgeries
-
Jejunostomy tube
- moderately invasive
- no aspiration risk
- long lasting
- can be used immediately post-op for almost any surgery
Parenteral Nutrition
-
Peripheral line (PPN)
- temporary
- non-invasive
- can provide up to 1/3 of nutritional requirements
- risk of local phlebitis/infection
-
Total parenteral nutrition (TPN)
- temporary or long term
- depends on type of central catheter
- minimally invasive
- can provide all caloric and nutritional requirements
- slows or stops catabolism
- may increase weight
- infection risk, hepatotoxiity
Treatment
for
N/V, anorexia, and taste alterations
-
Anti-emetic medications
- Zofran
- Compazine
-
Dietary Modifications
- beverages
- nutrient dense
- limited aroma
- cold, mild flavored foods
- high moisture foods
Treatment
for
Hepatic and Pancreatic Insufficiency
-
Diet modifications
- low fat diet
- branched chain AA
- probiotics
- reduce nitrogen production
-
Medications
- pancreatic enzyme replacement
- insulin
- lactulose
- acidify colon and reduce ammonias
Treatment
for
Immunosuppression
-
Diet
- maintain healthy food sources
- avoid uncooked meats
- increase 𝜔-3 FA intake
- increase Vit B and Folate
-
Mediations
- GM-CSF
- antibiotics
- vaccines
Neutropenic Diet
- Avoid all fresh fruits and vegetables, including garishes.
- Avoid raw or rare-cooked meat, fish, and eggs.
- Avoid salad bars, fruit bars, and deli-counters.
- Avoid raw nuts.
- All diary must be pasteurized.
- Avoid yogurt and products with live cultures.
- Safe food handling.
- Water
- may use tap
- bottled water must be reverse osmosis, distillation, or filtered through 1 micron or smaller
- well-water must be boiled for at least 1 min