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Neoplasms-DD exam 2 > Epidemiology of Cancer > Flashcards

Epidemiology of Cancer Flashcards

1
Q

What percentage of all malignant neoplasms are caused by environmental factors?

A

• 80% according to some studies

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2
Q

What is a classic example of regional differences in cancer rates suggesting environmental carcinogens?

A
  • Lung cancer in urban areas where particular industrial practices are done
    • Melanoma in sunny/warm states and in Colorado where UV exposure is high
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3
Q

How do researchers determine if a given cancer has an environmental cause?

A
  • Variations in incidence of specific types of cancer seen among different regions of a country (assuming fairly heterogenous population)
    • Variations in a given cancer in different countries around the world
    • Rates of incidence among people imigrating to an area vs. those native to that area
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4
Q

Using the example of Japanese-American immigrants, explain the dichotomy of enviromental and genetic differences in cancer pre-disposition?

A
  • Japanese have higher incidence of stomach cancer, Americans have higher incidence of colon and breast cancer
    • Immigrants, in 2-3 generations, adopt the host country’s cancer incidence trends
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5
Q

What are the three highest cancer death rates in males in the US?

A
  • Lung cancer = #1 (34%)
    • Prostate = #2 (12%)
    • Colon/rectum = #3 (11%)
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6
Q

What are the three highest cancer death rates for females in the US?

A
  • Lung (1) - 21%
    • Breast (2) - 18%
    • Colon/rectum (3) - 13%
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7
Q

What is the Denver-specific leading cancer killer in males?

A

• Lung cancer

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8
Q

What is the most common cancer diagnosed in Colorado women?

A
  • Breast cancer

* Over 12% of Colorado women will develop breast cancer by 75

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9
Q

What is the lifetime risk of prostate cancer for a dude in Colorado?

A
  • 1 in 5
    • For non-Hispanic whites 10% higher than US rate
    • For blacks, 13% LOWER than US rates
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10
Q

What are the four groups of compounds that are classically considered environmental carcinogens and what do they all have in common?

A 
• Polycyclic aromatic hydrocarbons
	• Aromatic amines
	• Nitrosamines
	• Aflatoxins
		○ All these need be "activated" into carcinogenic form by microsomal enzymes (CYP/P450 enzymes)
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11
Q

What are the unfortunate modifications that result in cytotoxicity and mutagenesis at the following atoms? (Carbon, Nitrogen, Sulfur)

A
  • Carbon - polycyclic aromatic hydrocarbons and the diol (epoxides)
    • Nitrogen - aromatic amines (aniline in dyes, 2-naphthylamine in rubber)
    • Sulfur - involved in industrial product formation
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12
Q

How are nitrosamines formed in the body?

A
  • 2-amines in food react with nitrous acid in stomach

* Microsomal hydroxylation leads to carbonium (cytotoxic) intermediates

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13
Q

What’s the deal with aflatoxins?

A
  • US exposure from moldy corn and wheat
    • Modly grains is main source
    • Cytotoxic after microsomal epoxidation
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14
Q

MOST chemical carcinogens are usually metabolized by what to become “active”? What do they do in the cell?

A
  • They are activated by microsomial (P450) enzymes into strong electrophiles
    • The ultimate worrying damage comes from RNA and DNA chemical modification
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15
Q

The chemical carcinogens that aren’t activated by microsomal enzymes work how?

A

• Dirctly modifying RNA and DNA
○ Alkylating agents
○ Acylating agents

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16
Q

What cancers are associated with the environmental exposure to:
• Metal vapors (industrial workers)

A

○ Nasal and lung cancers

17
Q

What cancers are associated with the environmental exposure to: • Arsenic exposure (old treatment of psoriasis)

A

○ Squamous carcinoma of skin

18
Q

What cancers are associated with the environmental exposure to: • Thorotrast (old contrast for radiologists)

A

○ Liver cancer

19
Q

What cancers are associated with the environmental exposure to: • Vinyl chloride (polymer industry)

A

○ RARE liver angiosarcoma

20
Q

What cancers are associated with the environmental exposure to: • Asbestos

A

○ Mesothelioma and lung cancer

21
Q

What cancers are associated with the environmental exposure to: • Benzene

A

○ Myeloid leukemia

22
Q

What cancers are associated with the environmental exposure to: • Radon gas

A

○ Lung cancer (esp. smoker)

23
Q

What is the Ames test and what does it show?

A
  • Centers around use of Salmonella thypimurium bacteria that are His (-)
    • Because they require added His to live, only a mutagen will make them live on their own
    • Bathe the bacteria with microsomal enzyme and the potential carcinogen
    • If you get His(+) clones on the agar, assume it’s a carcinogen that did it
24
Q

What is the sensitivity of the Ames test?

A
  • 90% of known carcinogens tested are Ames Positive

* Thus, 90% sensitive?

25
Q

Carcinogenesis requires what classic factors?

A
  • Time (more likely to get cancer as you age)
    • Cell proliferation (most cancers are epithelial in nature because of high division)
    • Cellular changes in DNA and RNA (need to be transmitted to daughter cells to compound the mutations)
    • Stem cells are most at risk for malignancy
26
Q

What are the two stages of cancer development? What stage does a carcinogen act in?

A
  • Initiation and promotion

* Carcinogens act at the initiation stage

27
Q

What are tumor promoters and how do they differ from carcinogens?

A
  • Promoters are not mutagens or carcinogens
    • Include phorbol esters, bile acids, saccharin, phenobarbital, butylated hydroxytolune, phenols
    • Often, promoters are irritants (cause inflammation)
    • Can act to stimulate cell division but not mutation
28
Q

What are special types of inflammation that can promote cancer? How?

A
  • Inflammation causes production of oxygen radicals and these can definitely cause mutations in DNA and RNA
    • Ulcerative colitis
    • Atrophic gastritis
    • Cholecystitis
    • Choseomyelitis
    • Schistosomiasis
    • Chronic hepatitis
29
Q

Xeroderma pigmentosum is a defect in what?

A

• Excision repair

30
Q

Ataxia-telangiectasis is a defect in what?

A

• dsDNA break repair

31
Q

Fanconi’s anemia is a defect in what?

A

• X-ray damage

32
Q

Inherited defects in mismatch DNA repair cause…?

A

• microsatellite instability and predispose to colon cancer

33
Q

What’s the carcinogen “general model”?

A
  • Environmental mutagens and oxidative damage to DNA result in genetic mutations that are inherited in daughter cells
    • Accumulation of mutations leads to chromosomal instability and the further predisposition for more mutations
    • Initial mutations, occuring in a rare stem cell create a “mutator” phenotype
    • The mutator phenotype is the stem cell that will eventually become the cancer cell (achieving the hallmarks)

Neoplasms-DD exam 2 (4 decks)

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