Topic 1 - Cancer Flashcards
Cause and mechanism
What is cancer?
A group of diseases that includes solid tumours at almost any site in the body, and leukaemias. A disease of the body’s own cells.
What causes cancer?
Uncontrolled division of abnormal cells in a part of the body
What are the features of cancer at a cellular level?
- uncontrolled cell division
- change in morphology
- dedifferentiation of cells
- cell mitigation into adjacent and distal tissues
What are the characteristics of cancer cells grown in lab?
- Uncontrolled growth
- Loss of contact inhibition
- Immortal
What are the stages of cancer development?
- Normal cells
- Hyperproliferative cell population
- Early adenoma
- Late adenoma
- Carcinoma
What is hyperproliferation?
An abnormally high rate of proliferation of cells by rapid division; substantial overproliferation
What is adenoma?
A benign tumour formed from glandular structures in epithelial tissue.
What are the steps of cancer development at a cellular level?
Normal cells Mutation Proliferation Mutation Rapid growth Tumour Mutation Malignant tumour Mutation Enters blood stream Metastatic tumour
What are the common genetic abnormalities?
- Point mutation
- Deletion
- Insertion
- Gene amplification
- Chromosomal translocation
- Aneuploidy
What can point mutations result in?
- A change in gene function
- Amino acid substitution
- Introduce a stop codon early
What can insertions and deletions result in?
- Gain or loss of one or two bases results in a shift in the reading frame of a gene transcript
- Frameshift mutation
What can gene amplification result in?
-A cell having anywhere up to 100 copies of a gene it would normally have 2 of
What can chromosomal translocations result in?
- Genes being moved to a more transcriptionally active site of the chromosome
- Two genes being recombined into a new gene fusion
What can aneuploidy result in?
-Any departure from the normal structure or number of chromosomes
What are the two things mutations can do to genes?
- Disrupt the coding sequence sufficiently to stop protein product from functioning normally
- Make the protein more active by improving the amino acid sequence, or by allowing more copies to be made
What does genetic instability caused by carcinogens/mutations lead to?
Genetic variation in populations of tumour cells for natural selection to work on
What does mutation induction require?
- Chemical modification of DNA
- Replication of DNA
- Resulting in misincorporation of DNA by polymerase
What induces normal cells to divide?
+ve growth factors
What prevents normal cells from dividing?
-ve growth factors
What is apoptosis?
The death of cells which occurs as a normal and controlled part of an organism’s growth or development
What are the characteristics of normal cells?
- Induced to divide by +ve growth factors
- Prevented from dividing by -ve growth factors
- Finite life span
- Self-destruct by apoptosis
- No influence on blood vessel formation
- Tightly joined and immobile
- Genetically stable
What are the hallmarks of cancer cells?
- Genetic instability
- Invasive and metastatic
- Independent of +ve growth factors
- Resistant to -ve growth factors
- Immortal
- Resistant to apoptosis
- Angiogenic
What is Angiogenesis?
The formation of new blood vessels
What are oncogenes?
Mutated versions of normal genes that have a key role in promoting growth and division of cells - mutations lead to increased activity/inappropriate switching on of cell division
What are tumour suppressor genes?
Genes that play a role in controlling growth/protecting cells against damage
What can cause cancer?
- Genetics
- Environmental agents (Biological, chemical and physical)
Give two examples of rare inherited cancer syndromes?
- Li Fraumeni syndrome
- Xeroderma pigmentosum
What are some biological causes of cancer?
- Hep B (liver cancer)
- HPV (cervical cancer)
- H. pylori (stomach cancer)
What are some chemical causes of cancer?
- Cig smoke (lung bladder etc, cancer)
- Heterocyclic amines in cooked meat (colon)
What are some physical causes of cancer?
- UV in sunlight (skin cancer)
- X-Rays/Gamma rays (radiotherapy related leukaemia)
What are carcinogens?
Agents that induce cancer:
- Any agent that significantly increases risk
- Often genotoxic
How do we show that a chemical is carcinogenic?
- Animal tests
- In vitro tests
- Epidemiological studies
What is a case control study?
Compares disease groups with matched control groups to look for factors more common in people with the disease
What are prospective studies?
Follow a population over time to confirm that the disease is linked to the suspected cause
What is a cohort study?
Healthy people are recruited and followed over time. Data collected about exposure is later used to establish whether there is an association between exposure and disease
What is an example of a carcinogen found in tobacco smoke?
Benzo[a]pyrene - binds to deoxyguanosine to form a DNA adduct. Adduct leads to increased chance of mutation
What is one form of DNA damaged caused by exposure of skin to UV?
Thymine dimer - the input of energy from the UV light causes the formation of covalent bonds between adjacent thymine molecules
