1. Molecular Biology Flashcards
1
Q
What is cancer?
A
- group of diseases characterised by unregulated cell growth and the invasion and spread of cells from the site of origin or primary site, to other sites in the body
2
Q
Describe Cancer Prevention
A
Process of taking action to lower the risk of getting cancer
- maintaining a healthy lifestyle
- avoiding or minimising exposure to known cancer causing substances
: physical, chemical, biological
- taking medicines or vaccines to prevent cancer from developing
3
Q
Describe preventable cancers with statistics (Cancer Research UK)
A
- 4 in 10 (42%) of cancer cases in the UK each year are linked to lifestyle factors
- in last 5 years, almost 600,000 cancer cases in the UK could have been prevented
- Cervical, mesothelioma, oral, larynx, oesophageal and lung cancers have the highest proportions of cases linked to lifestyle factors
- Prostate and testicular cancers have no established lifestyle factor links
- SMOKING is the largest single preventable cause of cancer in UK linked to estimated 19% of cancer cases in the UK each year
- Lung cancer has the highest proportion of cases linked to smoking
4
Q
What lifestyle changes can reduce cancer risk?
A
Smoking
- largest single preventable cause of cancer in UK, linked to estimated 19% of cancer cases in UK each year
Diet
- too little fruit, vegetables and fibre
- too much red and processed meat
- linked to an estimated 9% of cancer cases in UK each year
Overweight and Obesity
- linked to estimated 5% of cancer cases in UK each year
Alcohol
- linked to estimated 4% of cancer cases in UK each year
5
Q
How does smoking induce cancer?
A
- causes 28% of cancer deaths in UK and more than 4 in 5 cases of lung cancer
- associated with increased risk of several cancers, including lung, larynx, oesophagus, oral cavity and pharynx, bladder, pancreas, kidney, liver, stomach, bowel, cervix, leukaemia and ovarian cancers
- caused by direct effect on DNA including key genes that protect us against cancer e.g Benzene, polonium-210 along with other chemicals in cigarette smoke that inhibit DNA repair
- Scientists have found that the number of years you spend smoking affects your cancer risk even more strongly than the number of cigarettes you smoke a day
6
Q
How does Alcohol induce cancer?
A
- risk factor for many types of cancer (including oral, pharynx, larynx, oesophagus, liver, colorectal and breast)
- cancer risk increases with amount of alcohol
- risk for several cancer types increases if the person is a heavy smoker
- caused an estimated 6% of deaths worldwide in 2012, 13% of which were due to cancer
- reducing average alcohol intake in England by around 1 unit per person per day would avoid an estimated 8% of cancer deaths (Nichols, 2012)
7
Q
How does Physical inactivity (can include dietary factors and obesity) induce cancer?
A
- difficult to estimate the specific contribution of each of these risk factors and may underestimated the cumulative risk
- overweight and obesity are casually linked to several common cancers including oesophagus, colorectal, breast, endometrium and kidney
- taken together, raised body mass index and physical inactivity account for an attributable fraction of 19% of breast cancer mortaility, and 26% of colorectal cancer mortality
- obesity is the biggest cause of cancer after smoking. Estimated 1 in 20 cancers in the UK associated with being overweight
- Growing evidence to support reduced risk with weight loss
8
Q
Describe Infective causes of Cancer
A
- in 2012, approximately 15% of all cancers were attributable to infectious agents such as helicobacter pylori, human papilloma virus (HPV), hepatitis B and C, and Epstein-Barr virus
- Vaccines are available for hepatitis B virus and some types of HPV and can reduce risk of liver and cervical cancers, respectively
9
Q
Describe Human Papilloma Virus (HPV) with regards to cancer
A
- nearly all cervical cancers (99.7%) are caused by infection with a high-risk type of HPV, HPV infections are usually asymptomatic
- there are more than 100 different types of HPV
- most people will get HPV infection at some point in their lives and their bodies will get rid of it naturally without treatment but some women infected with a high-risk type of HPV won’t be able to clear it
- HPV (Types 6, 11, 16, 18) protects against 4 types of HPV (Types 16, 18, 6, 11). Between them, types 16 and 18 are the cause of most cervical cancers in the UK (More than 70%)
- Given to all girls in UK in year 8 then second dose 6-9 months later (vaccines)
10
Q
Describe how Environmental Exposure induces cancer
A
- pollution of air, water and soil with carcinogenic chemicals contributes to the cancer burden to differing degrees depending on the geographical settings
- outdoor air pollution is classified as carcinogenic, or cancer-causing, for humans. It has been estimated that outdoor air pollution contributed to 3.2 million premature deaths worldwide in 2012 including more than 200,000 lung cancer deaths
- additionally, over 4 million people die prematurely from illness attributable to the household air pollution from cooking with solid fuels, 6% of these deaths are from lung cancer
- indoor air pollution form coal fires doubles the risk of lung cancer, particularly among non-smoking women
- exposure to carcinogens also occurs via the contamination of food, such as aflatoxins or dioxins
11
Q
Describe how occupational exposure induces cancer
A
- more than 40 agents, mixtures and exposures circumstances in the working environment are carcinogenic to humans and are classified as occupational carcinogens
- occupational cancers are concentrated among specific groups of the working population, for whom the risk of developing a particular form of cancer may be much higher than for the general population
- it is well documented that occupational carcinogens are casually related to lung cancer, mesothelioma, and bladder cancer. For example, mesothelioma (cancer of the outer lining of the lung or chest cavity) is to a large extent caused by work-related exposure to asbestos
12
Q
Describe how Radiation causes cancer
A
- exposure to all types of ionising radiation, from both natural and man-made sources, increases the risk of various types of malignancy including leukaemia and a number of solid tumours
- Risks increase when the exposure occurs at a young age and also when the exposure amount is higher. UV radiation, and in particular solar radiation, is carcinogenic to humans, causing all major types of skin cancer, such as basal cell carcinoma (BCC), squamous cell carcinoma(SCC) and melanoma
- Avoiding excessive exposure, use of sunscreen and protective clothing are preventive measures, UV-emitting tanning devices are now also classified as carcinogenic to humans based on their association with skin and ocular melanoma cancers
- Residential exposure can also arise from radon, a naturally radioactive gas sometime present in soil and building materials increase risk of lung cancers.
Radon levels in homes can be reduced by improving the ventilation and sealing floors and walls
13
Q
What is Population Screening Programmes? Give examples of NHS population screening programmes
A
- Screening is process of identifying healthy people who may have an increased chance of a disease or condition
- The screening provider then offers information, further tests and treatment. This is to reduce associated problems or complications
Examples
- NHS breast screening
: all women aged 50-70
- NHS Bowel Cancer screening
: every 2 years to men and women aged 60-74
- NHS Cervical Cancer screening
: all women aged 24-49 every 3 years then 50-64 every 5 years
14
Q
What is cancer?
A
- Uncontrolled cell division
- Unregulation growth of abnormal cells, often inappropriate locations
- Depending on the locations, decides how easy it is to treat
- Most common treatment is removal by surgery, can afford to lose some tissues such as rectal or liver however places like brain is difficult to maintain normal function
15
Q
Describe hallmarks of cancer and examples of potential therapeutic methods to target them
A
- Sustaining proliferative signalling
- EGFR inhibitors - Evading growth suppressors
- Cyclin-dependent kinase inhibitors - Avoiding immune destruction
- Immune activating anti-CTLA4 mAb - Enabling replicative immortality
- Telomerase inhibitors - Tumour-promoting inflammation
- Selective anti-inflammatory drugs - Activating invasion & metastasis
- inhibitors of HFG/c-Met - Inducing angiogenesis
- inhibitors of VEGF signalling - Genome instability & mutation
- PARP inhibitors - Resisting cell death
- Proapoptotic BH3 mimetics - Deregulating cellular energetics
- Aerobic glycolysis inhibitors
16
Q
Describe naming of tumours
A
- Classified according to their embryonic tissue of origin
- Can recognise >200 tumour types
- Carcinomas
: arise from epithelial cells (90% cancers) - Adenocarcinoma
: arise from glandular tissue e.g breast - Sarcomas
: arise from connective tissue & muscle - Leukaemias
: blood cell-derived sarcomas
17
Q
Describe Benign tumour cells
A
- resemble normal cells
- tend to be localised
- often surrounded by a fibrous capsule
- usually require little treatment e.g warts
- surgical removal if appropriate
18
Q
Describe Malignant tumours
A
- often less well differentiated than normal cells
- grow and divide more rapidly
- high nucleus to cytoplasm ratio, fewer specialised structure
- more difficult to treat, less definition
- invade surrounding tissues
- enter circulation
: seed at a distant site (metastasis)
19
Q
Describe what ‘proto-oncogene’ is
A
- Normal function
: to control cell growth - Converted to oncogenes by gain of function mutation
: point mutation (always active)
: gene amplification (more protein)
: chromosomal translocation
20
Q
What are Oncogenes?
A
- a gene which in certain circumstances can transform a cell into a tumour cell
21
Q
What are Tumour Suppressor Genes?
A
- Genes which restrain cell growth, promote cell death and promote DNA repair
- Loss of function leads to excessive, unregulated growth of damaged cells
- Recessive genes
: both copies must be lost - Hereditary predisposition
: inheritance of one mutated copy of TSGene increases tendency of dev cancer
22
Q
Describe Epigenetics
A
- Modifications to genomic and chromatin components/structure
- Alter gene transcription and hence protein expression
- Heritable changes
- Usually involve histone modifications, methylation
23
Q
Describe molecular mechanisms of Cancer
A
Knudson, Vogelstein
- cancer cells usually contain 3-7 mutations
- cells undergoing a mutation must survive long enough to sustain subsequent mutations
- malignant transformation of a single cell is sufficient to give rise to a tumour
24
Q
What changes occur in the body that cause cancer?
A
- mutations in genes
- encoding proteins involved in regulation of cell growth and cell survival
25
Q
What causes the mutations?
A
- Chemical carcinogens (tobacco smoke, asbestos)
- Radiation ( U.V, Nuclear)
- Viruses (Human Papilloma Virus)
26
Q
Describe risk factors of Cancer
- Lifestyle
- Diet
- Reproductive life
A
Lifestyle
- environment, job
- Smoking accounts for 40% cancer deaths 1.18 million people
- Tobacco smoke contains 81 carcinogens
- UV, radiation exposure
Diet
- Eastern diet increased risk stomach cancer over western diet, Mediterranean best
Reproductive life
- Nuns have a higher risk of breast cancer but lower risk of cervical cancer
27
Q
Key points of Cancer (JUST READ)
A
- Cancer is a genetic disease
- Mutations occur in somatic cells
- Each cancer is a clone that arises from a single cell
- Multiple mutations are required >3
- Affects genes involved in growth control
- Proto-oncogenes and Tumour suppressor genes
28
Q
Describe Human Papilloma Virus (HPV)
A
- Oncogenic DNA virus
: integrates viral DNA into host genome - Permanently transforms host cells
- Causes warts and other benign epithelial growths
- Causes of cervical cancer (pap smear) (vaccine)
- E5 subunit causes prolonged activation of PDGFR
- E6 and E7 inhibit pRb and p53
29
Q
What are Epidermal Growth Factor Receptors?
A
- important proto-oncogenes involved in many cancers
- EGF important growth factor
: drives cell proliferation - Intrinsic kinase domain leading to activation of downstream signaling pathways
: Ras/ MAPK and PI3K-PKB - Mutations in receptor can cause
- Ligand independence
: constitutive dimerisation - Overexpression
: gene amplification
30
Q
Describe relation between HER2 and Breast cancer
A
The WT HER2 gene (ErbB2) is amplified in ~25-30% of metastatic breast cancers
Cells express 10-100x more Her2 receptor
HER2+ cells associated with more aggressive tumour phenotype and reduced survival rate
- cells grow faster
- tumours are more likely to recur
- correlates with more serious prognosis
31
Q
How is HER2 status detected?
A
IHC
- Immunohistochemistry
- staining with ab
- rating 0-3_ (latter deemed HER2)
Fish
- Fluorescent in situ hybridisation
- more sensitive than IHC
HER2-ECD ELISA
- detects cleavage product in serum
32
Q
What is Herceptin (Trastuzumab) (Roche)?
A
- Humanised monoclonal antibody recognising HER2 (recombinant molecule constructed by inserting murine CDR into human IgG)
- Herceptin binds HER2 and blocks its activity
- Phse 1 Clinical trials
: tumours grew more slowly some disappeared, provides significant survival benefit - Originally licensed for final stage aggressive HER2+ cancer
- Now also available to early stage patients
