Why And How Neoplasms Occur? Flashcards
What does carcinogenesis mean?
Causes of cancer
The causes of neoplasia is multifactorial, name some intrinsic and extrinsic factors that increase ones risk of getting cancers
Intrinsic: hereditary, age and gender (hormonal aspect)
Extrinsic: environment and behaviour (lifestyle)
*much of increased cancer incidence over the last century is due to prolonged life-span
List some behavioural/dietary factors that increase ones risk of getting cancer?
- high body mass index
- low fruit and vegetable intake
- lack of physical activity
- tobacco use (!!!)
- alcohol use
What is the Ames test?
A test that shows that initiators are mutagens while promoters cause prolonged proliferation in target tissue
What is a pro-carcinogen?
Substances that on their own are not carcinogenic,
Only when they are converted in the liver by cytochrome P450 (CYP450) enzymes do they become carcinogens
What is a complete carcinogen?
Substances that act as both initiators and promoters
Extrinsic factors account for approxiamately 85% of a population’s cancer risk. What are the three carcinogenic extrinsic factors categories?
Chemical
Radiation
Infection
Give some examples of malignant tumours that are effected by geographical variation
Breast
Gastric
Burkitt’s lymphoma
What are the 3 important things to note about the relationship between chemicals and malignant tumours?
- There is a long delay between carcinogen exposure and malignant neoplasm onset
- The risk of cancer depends on total carcinogen dosage
- There is sometimes organ specific you for particular carcinogens eg 2-napthylamine causes bladder carcinoma
Give some examples of chemical carcinogens (the initiators) (5)
- Polycyclic aromatic hydrocarbons
- Aromatic amines eg 2-naphylamine
- N-nitroso compounds
- Alkylating agents
- Natural products eg aflatoxin, asbestos
How deep does UV light penetrate?
No further than the skin
What does ionising radiation do? Give some examples of types
Strips electrons from atoms
X-rays, nuclear radiation (alpha and beta particles, gamma rays)
What is the most important type of radiation and why?
UV
Because we’re exposed to it daily and it can lead to increased skin cancer risk
In what ways can radiation cause DNA damage?
Direct: altered bases + dingle/double strand DNA breaks
Indirect: free radicals
How are we typically exposed to radiation?
UV=sunlight
ionising= radon (background radiation) + medical tests
What are the two types of radiation that we can experience?
UV light and ionising radiation
What are the ways in which an infection could be carcinogenic, either directly or indirectly?
Directly: affects genes that control cell growth
Indirectly: causing chronic tissue injury leading to regeneration of cells which act either as promoter for any pre-existing mutation or else causes new mutation from DNA replication errors
*they can also cause reduced immunity which allows other carcinogens to have a more profound effect
Which virus is strongly linked to cervical carcinoma?
HPV- human papilloma virus
How does HPV lead to carcinomas (cervical)?
It directly effects the gene expression within the cell
It expressed E6 which inhibits the action of the p53 protein- which means the following functions are inhibited: growth arrest, DNA repair and apoptosis
It also expresses E7 proteins which inhibit the action of the pRB protein which means the following functions are inhibited: excessive cell growth (due to inhibition of cycle progression until a cell is ready to divide)
How do Hep B and C viruses lead to carcinomas (indirectly)?
Both cause chronic liver cell injury and regeneration
Which acts either as a promoter for any pre- existing mutations or else causes new mutations from DNA replication errors
Name a bacteria that indirectly leads to neoplasms. Specify the type of carcinoma it may cause and how it does so
Helicobacer pylori
Causes chronic gastric inflammation which will lead to gastric carcinomas
Name a parasite that indirectly leads to neoplasms. Specify the type of carcinoma it may cause and how it does so
Parasitic flukes (flat worm)
Causes chronic inflammation in bile ducts and bladder mucosa
Increasing the risk of cholangiocarcinoma/ bladder carcinoma
How does Human immunodeficiency virus (HIV) cause neoplasms?
Indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur
Eg HHV8 leading to kaposi sarcoma
How does HBV lead to carcinomas (indirectly)?
Both cause chronic liver cell injury and regeneration
Which acts either as a promoter for any pre- existing mutations or else causes new mutations from DNA replication errors
What are tumour suppressor genes?
Genes that inhibit neoplastic growth
(Because they act like brakes on tumour growth, both alleles must be inactivated which explains why they need ‘two hits’ ie one for each allele)
What are oncogenes?
Genes that enhance neoplasticism growth
- abnormally activated versions of normal genes are called proto-oncogenes
- only one allele of each proto- oncogene needs to be activated to favour neoplasticism growth
What is the role of pRB?
Protein retinoblastoma
tumor suppressor protein whose main function is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide
What is the role of RAS?
It is a proto-oncogene that encodes plasma membrane signal transducers
What is c-NYC?
A proto-oncogene that encodes transcription factors
What is the role of HER-2?
It is a proto-oncogene that encodes growth factor receptors
What is the role of p53 in tumour suppression?
Tumour supression gene that has a role in growth arrest, DNA repair and apoptosis (cell death). The growth arrest stops the progression of cell cycle, preventing replication of damaged DNA
What is the role of caretaker genes?
They repair DNA damage
