Epidemiology of Cancer Flashcards
What percentage of all malignant neoplasms are caused by environmental factors?
• 80% according to some studies
What is a classic example of regional differences in cancer rates suggesting environmental carcinogens?
- Lung cancer in urban areas where particular industrial practices are done
- Melanoma in sunny/warm states and in Colorado where UV exposure is high
How do researchers determine if a given cancer has an environmental cause?
- 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
Using the example of Japanese-American immigrants, explain the dichotomy of enviromental and genetic differences in cancer pre-disposition?
- 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
What are the three highest cancer death rates in males in the US?
- Lung cancer = #1 (34%)
- Prostate = #2 (12%)
- Colon/rectum = #3 (11%)
What are the three highest cancer death rates for females in the US?
- Lung (1) - 21%
- Breast (2) - 18%
- Colon/rectum (3) - 13%
What is the Denver-specific leading cancer killer in males?
• Lung cancer
What is the most common cancer diagnosed in Colorado women?
- Breast cancer
* Over 12% of Colorado women will develop breast cancer by 75
What is the lifetime risk of prostate cancer for a dude in Colorado?
- 1 in 5
- For non-Hispanic whites 10% higher than US rate
- For blacks, 13% LOWER than US rates
What are the four groups of compounds that are classically considered environmental carcinogens and what do they all have in common?
• Polycyclic aromatic hydrocarbons • Aromatic amines • Nitrosamines • Aflatoxins ○ All these need be "activated" into carcinogenic form by microsomal enzymes (CYP/P450 enzymes)
What are the unfortunate modifications that result in cytotoxicity and mutagenesis at the following atoms? (Carbon, Nitrogen, Sulfur)
- Carbon - polycyclic aromatic hydrocarbons and the diol (epoxides)
- Nitrogen - aromatic amines (aniline in dyes, 2-naphthylamine in rubber)
- Sulfur - involved in industrial product formation
How are nitrosamines formed in the body?
- 2-amines in food react with nitrous acid in stomach
* Microsomal hydroxylation leads to carbonium (cytotoxic) intermediates
What’s the deal with aflatoxins?
- US exposure from moldy corn and wheat
- Modly grains is main source
- Cytotoxic after microsomal epoxidation
MOST chemical carcinogens are usually metabolized by what to become “active”? What do they do in the cell?
- They are activated by microsomial (P450) enzymes into strong electrophiles
- The ultimate worrying damage comes from RNA and DNA chemical modification
The chemical carcinogens that aren’t activated by microsomal enzymes work how?
• Dirctly modifying RNA and DNA
○ Alkylating agents
○ Acylating agents
What cancers are associated with the environmental exposure to:
• Metal vapors (industrial workers)
○ Nasal and lung cancers
What cancers are associated with the environmental exposure to: • Arsenic exposure (old treatment of psoriasis)
○ Squamous carcinoma of skin
What cancers are associated with the environmental exposure to: • Thorotrast (old contrast for radiologists)
○ Liver cancer
What cancers are associated with the environmental exposure to: • Vinyl chloride (polymer industry)
○ RARE liver angiosarcoma
What cancers are associated with the environmental exposure to: • Asbestos
○ Mesothelioma and lung cancer
What cancers are associated with the environmental exposure to: • Benzene
○ Myeloid leukemia
What cancers are associated with the environmental exposure to: • Radon gas
○ Lung cancer (esp. smoker)
What is the Ames test and what does it show?
- 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
What is the sensitivity of the Ames test?
- 90% of known carcinogens tested are Ames Positive
* Thus, 90% sensitive?
Carcinogenesis requires what classic factors?
- 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
What are the two stages of cancer development? What stage does a carcinogen act in?
- Initiation and promotion
* Carcinogens act at the initiation stage
What are tumor promoters and how do they differ from carcinogens?
- 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
What are special types of inflammation that can promote cancer? How?
- 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
Xeroderma pigmentosum is a defect in what?
• Excision repair
Ataxia-telangiectasis is a defect in what?
• dsDNA break repair
Fanconi’s anemia is a defect in what?
• X-ray damage
Inherited defects in mismatch DNA repair cause…?
• microsatellite instability and predispose to colon cancer
What’s the carcinogen “general model”?
- 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)
