Epidemiologic and Environmental Aspects of Cancer Flashcards
What percent of malignant neoplasms are caused by environment?
80%
T or F, migrants and their descendants adopt the relative risk of the country that they move to. What does this imply?
T.can’t attribute everything to genetics. Matters where you came from and where you go.
Identify the three most common types of cancer (other than skin cancer) among men (incidence).
Prostate- 26%
Lung- 14%
Colon/Rectum- 14%
Identify the three most common types of cancer (other than skin cancer) among women (incidence)
Breast- 29%
Lung-13%
Colon/Rectum- 8%
Identify the three most common types of cancer (other than skin cancer) among men (death).
Lung-28%
Prostate-9%
Colon/Rectum-8%
Identify the three most common types of cancer (other than skin cancer) among women (death).
Lung-26%
Breast-15%
Colon/Rectum-9%
An environmental chemical must be activated by what molecule to be considered carcinogenic?
P450
What are the four groups of chemical carcinogens?
- Polycyclic aromatic hydrocarbons (benzo(a)pyrene)
- Aromatic amines (anilines)
- Nitrosamines
- Aflatoxins
What are some examples of Polycyclic aromatic hydrocarbon carcinogens?
-benzo(a)pyrene-anything with a diol or epoxide group-at risk any time you burn stuff
What are some facts of Aromatic amine carcinogens?
- aniline
- requires N-hydroxylation and sulfation
- industrial and consumer products
What are some facts of nitrosamine carcinogens?
-carbonium intermediate-in preservatives in food (cheetohs)-2 amines in food react with nitrous acid in stomach
Where do aflatoxins come from?
- moldy grains, nuts, corn especially in tropics
- produced by aspergillus flavus
- microsomal epoxidation is required to be a carcinogen
If an epoxide is formed during a P450 reaction, _____
the product becomes cytotoxic and mutagenic.
Outline Miller’s theory of carcinogenesis
- CYP450 turns chemicals into active forms
- metabolites become strong electrophiles
- electrophilic species can chemically modify proteins, RNA, DNA
- The bases can be attacked and cause frameshifts and mispairings
P450 generates electrophiles which screw with RNA/DNA.
What is the Ames test?
A rapid and inexpensive test for mutagens. Tests ability to mutagenize Salmonella typhimurium.
Generally all carcinogens are mutagens but not all mutagens are carcinogens, T or F?
False:
Mutagens are carcinogens but not all carcinogens are mutagens.
A positive Ames test says what about the chemical?
it is mutagenic. It is assumed that it is already proven to be carcinogenic.
How does the Ames test work?
Media is lacking His and the is plated with lots of His negative bacteria. The bacteria needs His to grow. Apply carcinogen to central disk on agar; if some His+ bacteria start to grow it is assumed that the carcinogen did this and thus it is mutagenic.
T or F. Effect of a carcinogen is non-dose dependent in causing cancer
F
Is carcinogenesis a quick or lengthy process
lengthy, requires time
Carcinogens are specific to one type of cancer T or F?
T
Which tissues are at the most risk of carcinogenesis?
tissues that continually divide (epithelium, bone marrow)
The cellular triggers of carcinogenesis are _______. what does this mean?
stably inherited. Tumors are proliferations of clones of a malignant cell
T or F, only stem cells can become malignant.
T. Fully differentiated cells cannot become malignant
What are the two steps through which cancers develop?
- initiation
2. promotion
What is initiation?
the irreversible effect of the carcinogen
What is promotion?
A reversible step that requires the repeated application of a promoter (i.e. something that causes inflammation)
What is the difference between a carcinogen and a tumor promoter?
carcinogens cause mutations, tumor promoters drive proliferation without causing more mutations.
What happens if you reverse the order of cancer initiation and promotion.
Nothing. Think about the definitions of each.
Smoking is a carcinogen or promoter?
Promoter. it has phenols that cause inflammation?
How much time can be between initiation and promotion?
A long time. Skin cancer sometimes takes years to proliferate after it has mutated.
What are some common promoters?
urethan, phorbol esters, bile acids, saccharin, phenobarbitol, butylated hydroxytoluene phenols.
How do bile salts supports the idea that tumor promotion plays a role in development of human cancer?
they promote cancer in benign colon polyps in rats
What is evidence that tumor promotion plays a role in development of human cancers?
Former smokers lose increased risk of cancer after 14 yrs smoke free. if only apply carcinogen, don’t get proliferation of cancer.
Why is cancer more common among the elderly?
- 2 hit hypothesis (LoH)
- Lose tumor suppressors or gain oncogenes over time
- Cancers take time to develop
- Most are epithelial cancers (being old doesn’t put you at higher risk of every kind of cancer)
What is the difference between somatic and germline mutations?
S can’t be passed on while G mutations can be transmitted to offspring
Define epigenetic mutations.
These are not coded for in the DNA but are modifications that are added to proteins or DNA (as in methylation) that repress genes. They
How can epigenetic mutations cause cancer?
- methylation inactivates
- messes with reading
- they can silence a tumor suppressor
- loss of methylation can activate an oncogene.
