Chapter 3.2 Carcinogenesis Flashcards
What are carcinogens?
agents that damage DNA
oncogenic viruses
radiation can induce DNA damage
Aflatoxins are related to which carcinoma? Where do they come from?
important relationship to hepatocellular carcinoma
-derived from Aspergillus, which can contaminate stored grains
byproduct of Aspergillus would be aflatoxins which increase the risk of hepatocellular carcinoma
Alkylating agents increase the risk of what type of disease? Explain.
increase risk of leukemia/lymphoma
when we treat patients who have cancer with alkylating agent, one complication is increased risk of secondary lymphoma/leukemia years down the line (long term side effect of chemotherapy)
What cancers does alcohol cause? Explain the etiology.
related to squamous cell carcinoma of oropharynx and upper esophagus, pancreatic carcinoma, and hepatocellular
alcohol causes chronic pancreatitis which can lead to carcinoma
alcohol trashes liver, cirrhosis which increases risk for hepatocellular carcinoma
Exposure to arsenic leads to which cancers?
increases risk of squamous cell carcinoma of skin (women who used to work in England in field didn’t want people to see they had been working so they’d apply arsenic to skin which would lighten it; then they would develop squamous cell carcinoma
arsenic poisoning - test for it by clipping fingernails or remove hair and it can be found in fingernails and hair
increases risk for lung cancer (arsenic present in cigarette smoke)
angiosarcoma of liver
What two things can exposure to asbestos lead to? Which is more likely?
increases risk for lung cancer and mesothelioma (mesothelial cells of pleura)
exposure to asbestos is more likely to lead to lung cancer than mesothelioma !! IMPORTANT
What type of cancers does cigarette smoke lead to? Explain the etiology.
What is the most common carcinogen worldwide?
carcinoma of oropharynx, squamous cell carcinoma of esophagus, lung cancer, kidney and bladder (urothelium - kidney, bladder, ureters, part of urethra …key risk is cig smoke) carcinogens get into blood, filtered in kidney, concentrated in urine, hang out in bladder and entire collecting system is bathed in carcinogen constantly over period of years; key risk for kidney and bladder cancer
most common carcinogen worldwide; polycyclic hydrocarbons are particularly carcinogenic
(40 carcinogens in cigarette smoke but most important are polycyclic hydrocarbons)
What does the following carcinogen lead to?
Nitrosamines
Where is it found?
stomach carcinoma
found in smoked foods; responsible for high rate of stomach carcinoma in Japan
(intestinal type of stomach carcincoma or diffuse type… nitrosamines are related to intestinal type of stomach carcinoma and intestinal type is more common)
What does the following carcinogen lead to?
Naphthylamine
From what is this carcinogen derived?
urothelial carcinoma of bladder
derived from cigarette smoke
What does the following carcinogen lead to?
Vinyl chloride
Describe the population of patients most likely to be exposed.
angiosarcoma of liver (important study that det. this association; workers exposed and large amount developed this cancer)
occupational exposure; used to make polyvinyl chloride (PVC) (plastic type) for use in pipes
What does the following carcinogen lead to?
Nickel, chromium, beryllium, silica
lung carcinoma
occupational exposure
Describe the what exposure to the following oncogenic virus can lead to:
EBV
What is the typical patient affected? How does it present?
nasopharyngeal carcinoma, Burkitt lymphoma and CNS lymphoma in AIDS
classic patient is Chinese male or African individual,
classical presents at neck mass, metastasizes early to regional lymph nodes,
A Chinese male presents with a neck mass. Which oncogenic virus is most likely? What does this virus lead to?
EBV
nasopharyngeal carcinoma, Burkitt lymphoma and CNS lymphoma in AIDS
Describe the what exposure to the following oncogenic virus can lead to:
HHV-8
How do patients present?
What are the three patient subsets that are affected? Describe how to treat each.
karposi sarcoma (tumor of endothelial cells)
patients present with purple-ish raised lesions
patient subsets
1) older eastern European males -treatment is to excise the karposi sarcoma
- AIDS patients - treat virus by anti-retroviral agents to boost CD4 positive T cell count to allow immune system to destroy HHV-8 cells
- patients with transplants bc immunosuppressed - treat with reduces immunosuppression slightly to empower immune system to go kill those virally infected cells
Describe the what exposure to the following oncogenic virus can lead to:
Hepatitis B and C virus (HBV and HCV)
B- DNA virus
C- RNA virus
Hepatocellular carcinoma
Describe the what exposure to the following oncogenic virus can lead to:
HTLV-1
adult T cell leukemia/lymphoma
Describe the what exposure to the following oncogenic virus can lead to:
High risk HPV (16, 18, 31, 33)
squamous cell carcinoma of vulva, vagina, anus and cervix; adenocarcinoma of cervix
What type of cancer does ionizing (nuclear reactor accidents and radiotherapy) radiation lead to?
What is the mechanism?
AML, CML, papillary carcinoma of thyroid (children exposed to Chernobyl accident)
mechanism: generates hydroxyl free radicals (water within tissues hits with ionizing radiation and byproduct is hydroxyl free radicals)
What is the most common cause of non-ionizing radiation?
UVB sunlight is most common course
Non-ionizing radiation leads to what type of cancers? Explain the mechanism.
basal cell carcinoma of skin, squamous cell carcinoma of skin, melanoma of skin
results in formation of pyrimidine dimers (nicks in DNA) which are normally excised by restriction endonuclease, excessive exposure will produce exceessive damage and overrun ability to respond to damage
What does xeroderma pigmentosum lead to? Explain the mechanism.
xeroderma pigmentosum is mutation of restriction endonucleases that excise formation of pyrimidine dimers in DNA
without these endonucleases the dimers form and DNA damaged and not repaired; leads to basal cell carcinoma, squamous cell carcinoma, and melanoma of skin
What are the three key systems that can be disrupted by carcinogenic agents?
DNA mutations eventually disrupt key regulatory systems
allows for tumor growth and progression
- proto-oncogenes
- tumor suppressor
- regulators of apoptosis
What are proto-oncogenes?
essential for cell growth and differentiation
mutations form oncogenes
lead to unregulated cell growth
What are the 5 categories of proto-oncogenes?
growth factors growth factor receptors signal transducers nuclear regulators cell cycle regulators