mechanisms of oncogenesis Flashcards
cancer statistics
incidence = someone is diagnosed every 2 mins in UK
990 cases diagnosed everyday
mortality = every 4 mins someone dies from cancer
risk = 1 in 2 people in Uk will be diagnosed with some form of cancer during their lifetime
cancer survival and prevention
survival = half of diagnosed survive for 10 years
prevention= 4 in 10 cases linked to lifestyle
prevention and reducing risks
smoking hormones obesity and weight alcohol workplace causes of cancer sun and UV infections and HPV physical activity diet and healthy eating inherited genes air pollution and radon
what is cancer
name for a group of diseases characterised by:
abnormal cell proliferation
tumour formation
invasion of neighbouring normal tissue
metastasis to form new tumours at distant sites
over 200 diff types of cancers
approx 85% occur in epithelial cells = carcinomas
cancers derived from mesoderm cells = sarcomas
cancers found in glandular tissue = adenocarcinomas
hallmarks of cancers (6)
two enabling characteristics = genome instability and tumour inflammation
two emerging hallmarks = avoiding immune destruction and reprogramming energy metabolism
- resisting cell death
- deregulating cellular energetics
- sustaining proliferative signalling
- evading growth suppressors
- genome instability and mutation
- inducing angiogenesis
- activating invasion and metastasis
- tumour promoting inflammation
- enabling replicative immortality
- avoiding immune destruction.
evidence suggesting cancer is a disease of the genome at cellular level
- carcinogens cause alterations to DNA
- DNA from tumours contain many alterations from point mutations to deletions
- many mutations over time = multi step process underlying carcinogens
- accumulation occurs openly after cells defence mechanism of DNA repair been evaded
- in cases if severe damage cell apoptosis induced
- mechanisms exist for blocking carcinogenesis but over burdening system increases possibility that cells will escape surveillance
longer we live = more time for DNA to accumulate mutations that may lead to cancer
cancer is more prevalent as lifespan has increased
evidence that cancer is a disease of the genome at the cellular level
tumour cells:
somatic mutations constitute all mutations in tumour cells
all cells in primary tumour arise from single cell, initiation of development of cancer is clonal
only one of the 10^14 cells in body need to be transformed to create a tumour
continued accumulation of mutations
tumour cells can evolve sub clonal selection allowing growth advantage and explain and heterogeneity of cells in tumour
dependent on interaction with other tumour cells and tumour clonal cells microenvironment
conversion of a normal cell to tumour cell
proliferation and control = control of cell division within a tissue is important in rapidly self renewing tissues when proliferation must balance cell loss
signals = messages, growth factors, EGF, PDGF,
cytokines: growth hormone, interleukins
hormones: oestrogen
oncogenes and tumour suppressor genes
- normal genes regulate growth
- normal genes can be activated to be oncogenic are called proto-oncogenes
- oncogene = protooncogene that has mutated in a way that leads to signals that cause uncontrolled growth, cancer.
tumour suppressor genes = inhibit both growth and tumour formation. act as braking signals during phase G1 of cell cycle, stop or slow cell cycle before S phase
- if tumour suppressor genes are mutated, normal brake mechanisms disables = uncontrolled growth
multistage carcinogenesis
3 assumptions:
- malignant transformation of single cell is sufficient to give rise to a tumour
- any cell in a tissue is as likely to be transformed as any other of the same type
- once a malignant cell is generated the mean time to tumour detection is generally constant
chemical carcinogens
cancer = 3 steps = initiation, promotion, progression
chemical carcinogens can alter these processes to induce their carcinogenic effects
presence of multiple mutations in critical genes is a distinctive feature of cancer cells and supports that cancer arises through accumulation of irreversible DNA damage
in majority of instances chemical carcinogens can induce this DNA damage and act in genotoxic manner
several classes of carcinogens
chemical = 10 groups: polycyclic aromatic hydrocarbons, aromatic amines, azo dyes, nitrosamines, carbamates, halogenated compounds, alkylating agents
physical = radiation and asbestos
heritable = predisposition
viral = hepatits B and epstein Barr
cancer causing chemicals in tobacco and cig smoke have other uses too…
Benzene – an industrial solvent, refined from crude oil
Arsenic – a poison, used in wood preservatives
Cadmium and lead – used in batteries
Formaldehyde – used in mortuaries and paint manufacturing
Polonium-210 – a highly radioactive element
Chromium – used to manufacture dye, paints and alloys
1,3-Butadiene – used in rubber manufacturing
Nickel – used to protect metals from corrosion
Vinyl chloride – used to produce plastic and vinyl products
Beryllium – used in nuclear reactors
chemical carcinogens
Four of the major groups polycyclic aromatic hydrocarbons, aromatic amines, nitrosamines and alkylating agents
exert their effects by adding functional groups to DNA bases called DNA adducts
One example is coal tar, which contains benzo[a]pyrene, a polycyclic hydrocarbon
Benzo[a]pyrene is commonly found in cigarette smoke (together with 81 other carcinogens)!
describe ames test
a test to determine the mutagenic activity of chemicals by observing whether they cause mutations in sample bacteria
