Cancer (ch 20) Flashcards
What percentage of Canadians will be diagnosed with cancer? Of that group, what percentage will die from it?
50% will be diagnosed and of these, 25% will die.
What percentage of deaths in Canada are reported to be due to cancer?
~30%.
What civilization was the first to treat cancer?
Ancient Egypt, treated with cauterization. Who would’ve thought?
Which Canadian province has the lowest incidence of cancer? What about the highest? Why might this be?
Lowest: BC
Highest: Nunavut
Probably due to lifestyle but maybe also a genetic component (Nunavut has large First Nations population).
What is an example of an environmental factor that has been shown to be causally linked to cancer?
Light at night (honours project woot woot).
Is the rate of cancer deaths projected to continue increasing in Canada?
No, it’s pretty much leveled off. Still increasing, but in proportion to population growth.
What might be a reason why cancer incidence rates are projected to increase over the next 20 years?
Risk of cancer increases with age, as there is a greater chance of accumulating gene mutations over time. Because we predict an ageing population, we also predict increased cancer incidence.
With regards to cancer pathology, what does TNM mean?
Tumour, Node, Metastasis.
Describe a Stage 0 cancer diagnosis.
A group of abnormal cells with the potential to develop into cancer in the future.
Describe a Stage 1 cancer diagnosis.
The cancer is small and contained within the organ it first started growing in.
Describe a Stage 2 cancer diagnosis.
The tumour is growing, but has not invaded other tissues. May have spread into adjacent lymph nodes.
Describe a Stage 3 cancer diagnosis.
The tumour is large and has invaded surrounding tissues and lymph nodes.
Describe a Stage 4 cancer diagnosis.
The cancer growth is advanced and has spread through the blood/lymph to distant sites in the body (i.e. metastatic cancer).
Why are some cancers detected earlier than others?
Some have common screening practices (breast, cervical) or are visually apparent (skin). Others are not screened for (lung) or are hard to diagnose.
Why is lung cancer more likely to be fatal than other cancers?
Because it is not screened for and often is not detected until it is in an advanced stage.
How many cells must make up a tumour before it is visible on x-ray?
10⁸ cells.
How many cells must make up a tumour before it becomes palpable (if possible)?
10⁹ cells.
How many cancer cells (on average) will lead to the death of a patient?
10¹² cells.
The incidence of _____ cancer has been increasing since 1985. What is this likely the result of?
Liver cancer. Results from chronic hepatitis infections as well as alcoholism, obesity, diabetes, smoking (obesity epidemic?).
How was it determined that stomach ulcers (a cause of stomach cancer) were the result of bacterial infection?
Cause of ulcers confirmed when Barry Marshall drank some Helicobacter pylori, developed ulcers, and then treated them with antibiotics. What a mad lad!
Why is it not practical to screen everyone who has stomach ulcers for cancer?
Because there’s a lot of people with ulcers but only a few of them will get cancer.
What are some viruses which are known to increase the risk of cancer?
Hepatitis, HIV, HPV etc.
What is a carcinoma?
A cancer arising from epithelial tissue. Common because epithelium replicates more frequently than other cell types, giving more chances for mutation.
What is a sarcoma?
A cancer arising from muscle and connective tissues.
What is the most common type of cancer? Why?
Carcinomas are the most common because epithelium replicates more frequently than other cell types, giving more chances for mutation.
What is a Leukemia/Lymphoma?
A cancer of the white blood cells/lymphocytes.
What 2 failures of proliferation can lead to tumour growth?
- Increased cell division but normal apoptosis
2. Normal cell division but decreased apoptosis
What differentiates a benign and a malignant tumour?
Benign: localized, don’t invade other tissues
Malignant: metastatic growth, invasion
How can cancers subvert normal replicative cell senescence?
By hijacking telomerase to keep adding to the telomeres.
What percentage of cancer deaths are the result of metastatic cancer?
~90%.
What fraction of cells survive metastasis to grow in a new area of the body?
1/1000. Those that do have enhanced survival ability and pass that on to the new tumour and future metastases.
What are the 2 difficult barriers to cancer metastasis? What is the 1 easy barrier?
Difficult:
- Escape parent tissue
- Colonize remote site
Easy:
1. Travel through circulation
Define “cooptive growth” as it relates to cancer.
A tumour exploiting existing blood vessels for nourishment.
Define “angiogenic growth” as it relates to cancer.
A tumour creating its own blood vessels for nourishment.
What percentage of tumour cells have the capacity to form a new tumour?
~1%.
What is a “transit amplifying cell” with regards to cancer?
A tumour cell which has limited self-renewal capacity and will eventually die. Contrast with cancer stem cells which propagate indefinitely.
Approximately how many genes must have mutations before cancer is likely to develop?
At least 5 different genes.
Are tumours made up of only one kind of cell?
No, in addition to cancerous cells they can have endothelial cells, pericytes, etc. which support growth.
How many cell divisions happen in the human body over the course of an average lifetime? What fraction of these cause a mutation?
10¹⁶. Only 1 in a million cause a mutation.
In what 3 ways might genes be heritably inactivated, giving rise to cancer?
Accidental…
- Change in nucleotide sequence
- DNA packaging into heterochromatin
- Methylation of C nucleotides
Are epigenetic changes to the genome heritable over generations? What is a caveat to this?
No. However, one cell can pass them to another cell through cell division.
With regards to cancer pathology, what best describes a “driver” mutation?
A mutation in the cancerous cells which confers an ability of some kind or allows the cancerous cells to bypass some constraint.
With regards to cancer pathology, what best describes a “passenger” mutation?
A side effect of genomic instability. Not conferring any advantage on the cancerous cells
What are some examples of known carcinogens?
Arsenic, Asbestos, Aflatoxin, Ethidium Bromide, Radiation, etc.
With regards to cancer pathology, what is the purpose of the Ames test?
To test whether a substance is a potential carcinogen.
Describe the Ames test for potential carcinogens.
Mix His-dependent culture, compound, and liver extract. After incubation, stronger carcinogens will have caused more cells to become His-independent.
Why is liver homogenate added to the culture used in the Ames test for potential carcinogens?
Carcinogens are often not harmful until they’ve been metabolized by the liver, so we add this to simulate biological conditions.
Give an example of a known marker for chronic myeloid leukemia (CML).
The Philadelphia chromosome!
In cancer pathology, do overactivity mutations have a dominant or recessive effect?
Dominant. A single mutation event creates the oncogene.
In cancer pathology, do underactivity mutations have a dominant or recessive effect?
Recessive. Two mutations are needed to functionally deactivate the tumour suppressor gene.
In what 4 ways can a proto-oncogene become an oncogene?
- Deletion/point mutation in coding sequence
- Mutation in regulatory sequence
- Gene amplification
- Chromosome rearrangement
How can a deletion or point mutation in a gene’s coding sequence cause cancer?
By creating an abnormally hyperactive or constitutively expressed protein product.
How can a mutation in a gene’s regulatory sequence cause cancer?
By greatly overexpressing the protein product.
How can a gene amplification event cause cancer?
By greatly overexpressing the protein product.
In what 2 ways can chromosome rearrangement cause cancer?
- Overproduction due to nearby regulatory region
2. Overproduction due to fusion with actively transcribed gene
How are cancer cells most easily identified in culture?
They lost contact inhibition and start to grow all on top of one-another.
How can we differentiate the energy production method of normal differentiated cells and cancer cells?
Normal: prefer oxidative phosphorylation for energy
Cancer: strongly favour lactate for energy
What does the Warburg effect stipulate with regards to cancer pathology?
That cancer cells prefer to derive energy from lactate rather that the more efficient oxidative phosphorylation.
Why is it far less common for people to develop a retinoblastoma in only one eye as opposed to both? Answer in terms of hereditary cancers.
Requires a double knockout (rare). However, many people who inherit a knockout of one gene will have retinoblastoma in both eyes because it only took one more knockout.
If a maternal copy of a gene is already non-functional, what are some ways in which the paternal copy can be eliminated?
- Nondisjunction (chromosome loss)
- Loss then duplication (2 mutant copies)
- Mitotic recombination
- Gene conversion
- Deletion
- Point mutation
Just know that the loss of tumour suppressor gene function can be from a combination of genetic and epigenetic changes.
Couldn’t think of a question, just know that it could be 2 epigenetic changes, 2 genetic changes, or a combination of both.
When was the human genome sequence performed?
2000.
From cancer genome sequencing, what comparisons can be made between oncogenes and tumour suppressor genes in terms of susceptibility to mutation?
Oncogene: many missense mutations in a few key areas
Tumour Suppressor: truncating mutations all over, missense mutations localized around regulator binding site
What cancer does Imatinib (Gleevec) treat? How?
Chronic Myelogenous Leukemia (CML). Inactivates oncogenic kinase, preventing it from phosphorylating target.
What intracellular signalling pathway is a common target for inhibitory anti-cancer drugs? What parts of this pathway are targeted?
The Ras-MAP kinase pathway. Almost all parts of the pathway are targeted (Receptor, Ras, Raf1, Mek, Erk, etc.)
Why is multidrug treatment a common approach in cancer therapy?
A cell may be resistant to drug A or drug B. The cells have the potential to become resistant to A and B unless both are given simultaneously.
How can immunological therapy be used to treat cancer?
By injecting antibodies that selectively target and poison cancer cells. Can also remove the immunosuppressive tumour environment.
What can a sequence of a genome show us with regards to cancer pathology?
Whether there are gene amplifications (of new oncogenes) or gene deletions (of tumour suppressors).
What will a DNA microarray show when used to identify cancer? What else is required?
Need to fluorescently label the normal and tumour tissue. Then on a microarray we can see distinct fluorescence in parts of the genome corresponding to cancerous or normal DNA.
What are some examples of oncogenes?
- Myc
- IDH1 (isocitrate dehydrogenase 1)
- FOXL2 (transcription factor)
What 2 methods are most often used to identify tumour suppressor genes?
- Microarray analysis of healthy vs tumour tissue
2. Studying rare hereditary cancers
What is the Philadelphia chromosome?
An aberrant chromosome associated with CML which is the result of faulty chromosomal translocation between chromosomes 9 and 22.
