PTN - Nutrition and Cancer (DellaValle)

Question 1

Which stage of carcinogenesis is involved with molecular changes that start the path towards generating malignancy?

Answer 1

Initiation

Question 2

Promotion, the second stage of carcinogenesis, is characterized by events that contribute to ______ and ______ of cancerous cells?

Answer 2

Growth and proliferation This stage involves mutations that activate oncogenes or inhibit tumor-suppressor genes, which allows the cell to proliferate and grow into a tumor without regulation.

Question 3

What term is used to describe cancerous cells that have migrated to other locations in the body?

Answer 3

Malignancy

Question 4

What are the 4 stages of carcinogenesis?

Answer 4

1. Initiation - molecular changes that start the path towards generating a malignant tumor cell
2. Promotion - events that contribute to proliferation of tumor cells and their growth into a microscopic tumor in situ
3. Progression - further growth and spreading within the originating tissue
4. Metastasis - spreading of the tumor cells to other sites

Question 5

Besides diet, what are the 3 primary causes of cancer in humans?

Answer 5

1. Radiation
2. Free-radical damage
3. Adduct-forming chemicals

Question 6

True or False: Diet can impact whether or not cancerous cells are eliminated or progress to metastatic disease.

Answer 6

True

Diet can cause a 50-70% increase in risk of developing malignancy

Question 7

Describe the stages of malignancy.

Answer 7

1. Initial mutation causes cell to proliferate into more cancer-prone cluster
2. Cells from initial cluster acquire their own mutations and grow into separate clusters
3. Newly malignant cells develop mutations that interfere with normal cell growth checkpoints

Question 8

How can a tumor-suppressor gene mutation induce cancer?

Answer 8

Tumor-suppressor genes normally inhibit cell growth and proliferation.

Mutations of both alleles of a tumor-suppressor gene are required for carcinogenesis. Inactivation causes unregulated cell proliferation and acquiring of mutation.

Question 9

What are mutator genes and how are they involved in carcinogenesis?

Answer 9

Mutator genes reduce the ability of cells to prevent or repair damaged genes.

Changes to mutator genes can lead to propagation of mutations and dysregulation of cell cycle checkpoints, allowing for unrestricted growth.

Question 10

Which of the following compounds is likely to produce a biologically significant antioxidant effect?

A. Vitamin D

B. Calcium

C. Ascorbic acid (vitamin C)

D. Magnesium

Answer 10

C. Ascorbic acid

Ascorbic acid is able to donate an electron to free-radicals (oxygen compounds with an extra, unpaired electron) to stabilize them.

Vitamin C also helps to convert tocopherol quinine (a toxic intermediate) back into alpha-tocopherol

Question 11

Describe the conversion of the superoxide anion (O₂^-) into non-toxic substances that can be excreted by the body.

Answer 11

Superoxide is converted into hydrogen peroxide via superoxide dismutase

Hydrogen peroxide is converted into water and oxygen via catalase

Question 12

Which free radical is highly toxic in the presence of iron or copper?

Answer 12

Hydroxyl radical

Question 13

What is the general mechanism that carcinogens cause cancer?

Answer 13

Carcinogens typically react with DNA and modify it, which leads to mutations.

Question 14

Name the three main types of carcinogens mentioned in the module.

Answer 14

1. Nitrosamines
2. Polycyclic aromatic hydrocarbons
3. Heterocyclic amines

Question 15

Why is dietary fiber considered to be protective against the development of cancer?

Answer 15

Dietary fibers bind polycyclic aromatic hydrocarbons and other carcinogens and cause them to be excreted from the body more rapidly than they normally would.

Fibers also act as a bulking agent to reduce carcinogen concentration in the intestines.

Question 16

How do phase I and phase II liver metabolism enzymes play a role in carcinogenesis?

Answer 16

• Phase I Enzymes
  
  • Responsible for activating carcinogenic compounds (via hydrolysis)
    
    • Hydroxyl group can interact with bases to form DNA adducts
    • Ex: NNK (chemical from smoke)
• Phase II Enzymes
  
  • Conjugate carcinogens with molecules (glutathione/glucuronic acid) to promote excretion in urine
  • Phase II activating compounds present in RAW fruits and vegetables
    
    • Ex: isothiocyanates, organosulfur compounds

Question 17

Mrs. Sedgely is an obese 52-year-old black woman who works as a domestic housecleaner and has a seventh-grade education. Her mother just died of breast cancer at the age of 69 and she wants to know what she can do to prevent getting cancer.

What are her major risk factors for developing cancer?

Answer 17

1. Ethnic background - African Americans are more likely to get cancer
2. Body weight - obesity causes increased production of insulin and estrogen, which causes:
   
   1. DNA damage
   2. Increased cell proliferation
   3. Decreased apoptosis
3. Family history - some cancers have a genetic component
4. Socioeconomic background - cheap processed foods contain nitrites, which can cause cancer

Question 18

True or False: Growth factors bind Ras proteins in cell membranes and activate them, causing cell growth.

Answer 18

True.

Mutations in these growth factor receptors (G-protein coupled receptors) cause constitutive activation of Ras –> uncontrolled cell growth

Question 19

How do monoterpenes (from fruit consumption) decrease the progression of slow-growing cancers?

Answer 19

Monoterpenes are compounds that inhibit farnesylation, a normal process that anchors gene products to cell membranes.

By interfering with this, monoterpenes decrease the number of active Ras in the cell membrane. This disrupts excessive signaling and decreases cell proliferation and growth.

Question 20

What are the roles of hormone-like vitamins and physotestrogens in halting tumor cell progression?

Answer 20

1. Hormone-like vitamins - retinoic acid (vitamin A) and vitamin D
   
   1. Dimerize with steroid hormone receptors in the cytoplasm to induce gene expression
   2. Gene expression –> cell differentiation and induces cell cycle arrest
2. Phytoestrogens - genistein and isoflavones
   
   1. Bind to estrogen receptors, but elicit a weaker response than normal estrogen
   2. Acts as a competitive inhibitor of estrogen, leading to decreased growth of tumors in ovary, breast, and prostate
   3. Found in: soy beans and legumes

Question 21

What are 3 dietary factors that can strengthen immune function?

Answer 21

1. Low-energy/low-fat diet
2. High omega-3 to omega-6 ratio
3. Adequate intake of vitamins, carotenoids, and trace minerals (selenium, zinc)

Question 22

How can obesity lead to cancer?

Answer 22

1. Obesity can lead to high blood sugar and high nutrient content, which increases IGF-1, leading to activation of mitogens and growth factors
2. Obesity increases production of insulin and estrorgen:
   
   1. Damages DNA
   2. Increases cell proliferation
   3. Decreases apoptosis

Question 23

What are the top 3 recommendations that you can give to your non-vegetarian patient if he/she wants to try to decrease risk of cancer?

Answer 23

1. Increase daily fruits and vegetables - at least 5 servings/day
2. Become more physically active - at least 30-60 minutes of moderate exercise a day
3. Reduce intake of red and processed meats