Flashcards in Epidemiology of Cancer Deck (33)
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
○ 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
• Chronic hepatitis
Xeroderma pigmentosum is a defect in what?
• Excision repair