Cancer

Question 1

What is cancer?

Answer 1

When abnormal cells divide in a uncontrolled way.
Most cancers start due to gene changes that happen over a persons lifetime. Cancers can also start due to faulty genes passed down in families.

Usually starts from a change on a pro-oncogene.

Question 2

What are primary and secondary tumours?

Answer 2

Primary –> first mutation
Secondary –> metastasis (spread from primary)

Question 3

What influences prevalence of cancer?

Answer 3

Prevalence increases with age
- more likely for cell division of mutated genes
Gender –> more common in males

Question 4

What is the most common type of cancer for each gender?

Answer 4

Females:
1. Lung & bronchus 26%
2. Breast 15%
3. Colon & rectum 9%
4. Pancreas 7%
5. Ovarian 6%
6. Non-Hodgkin Lymphoma 4%

Males:
1. Lung & bronchus 28%
2. Prostate 11%
3. Colon & rectum 8%
4. Pancreas 6%
5. Liver & intrahepatic bile duct 4%
6. Leukaemia 4%

Question 5

What regulate cell growth?

Answer 5

Transcriptional factors, proteins, hormones e.g. growth factors.

Insulin at membrane receptor –> stimulate intracellular proteins –> up-regulate transcriptional factors in nucleus.
Some transcriptional factors can stimulate the synthesis of proteins, e.g. GLUT-4 transporter protein –> glucose uptake
Can also stimulate transcriptional factors to induce cell division - semi-conservative process (includes a copy from the original gene)

Question 6

How can cell division lead to cancer?

Answer 6

During mitosis, DNA replication is a semi-conservative process meaning a copy of the original DNA is inserted into the new DNA. If there is any damage in the original gene this will be passed to the replicated gene. As it divides further more and more cells will have this damage/ mutation which can accumulate and over time form a tumour.

Question 7

Where does a mistake occur in mitosis with cancer?

Answer 7

In DNA synthesis (S phase - interphase)
- When this process doesn’t work properly cancer cells don’t get destroyed.

A gene with damage or mutation does not go through apotosis during mitosis as the DNA synthesis phase. Meaning the cell carries out replication despite not being a healthy cell.

Question 8

What is differentiation?

Answer 8

Most adult cells are differentiated - they have become specialised in structure and function.
Non- differentiated cells are not functional –> accumulation can compromise organ function.

Immune cells are made in the bone marrow where they are released as stem cells where they differentiate into the cells that is required in the body, e.g. macrophages, white blood cells.

Question 9

What are cancer cells?

Answer 9

Undifferentiated cells
- dispersed organelles
- not able to support the main activity a normal cell carries out e.g. in liver, cannot carry out liver function.

If there are few undifferentiated cells in an area, the function can usually still be carried out by other cells. The accumulation of the undifferentiated cells in a large number, can compromise the normal function of the organ.
Can be reflected through cancer symptoms, e.g. pain, elevated inflammatory markers

Question 10

What are the 2 key properties of cancerous cells?

Answer 10

1. Capacity for perpetual cell division
   - loss of regulation and control of cell division
   - division occurs at a much more rapid rate
2. Loss of ability to undergo apoptosis
   - mutations accumulate over time
   - cells not identified during mitosis

Question 11

What is a benign tumour?

Answer 11

A growth that is not cancer
Hyperplasia of abnormal cells
Doesn’t invade nearby tissue or spread to other parts of the body - contained to the tumour
Don’t affect organ function/ activity
Cells still functional
Grow slowly

e.g. polyps in ulcerative colitis - mass of intestinal cells which isn’t affecting the normal colon function –> important to remove as the cells can mutate and divide more quickly and induce non-differentiated cells which can lead to colon cancer.

Question 12

What is angiogensis?

Answer 12

Undifferentiated cells increase flow of blood close to the tumour to help with growth and live from increased oxygen.
Cancer cells release growth factors to increase the number of blood vessels close to the cells.

Tumoural cells are also able to enter the blood stream where they are then at risk of creating secondary tumours as they can spread to other areas of the body

Question 13

What is metastasis?

Answer 13

Presence of tumoural cells in another part of the body/ secondary organ.
Spread of cancer from primary to secondary.
Can occur from angiogenesis, when have an increased ability of entering the bloodstream to travel to other tissues and parts of the body.

Harder to treat

Question 14

What are malignant tumours?

Answer 14

Formed by embryonic, primitive or poorly differentiated cells. They grow in a rapid, disorganised manner that is harmful to the body. They can also invade surrounding tissues and become metastatic, initiating the growth of similar tumour in distant organs

Question 15

What are carcinomas?

Answer 15

The most common type of cancer
- arise from cells that cover external and internal body surfaces e.g. lung, breast and colon

Question 16

What are sarcomas?

Answer 16

Affect tissues of the body such as bone, cartilage, fat, connective tissue and muscle

Question 17

What are lymphomas?

Answer 17

Cancer that affects lymph nodes and tissues of the body’s immune system

Question 18

What are leukaemias?

Answer 18

Immature blood cells that grow in the bone marrow and tend to accumulate in large numbers in the bloodstream

Compromises the immune system

Question 19

What are the 4 stages of cancer development?

Answer 19

1. Uncontrolled cell proliferation
2. Loss of apoptosis
3. Angiogenesis –> release growth factors to increase blood flow to tumour to increase oxygen and nutrient supply to further support cell division and growth.
4. Tissue invasion and metastasis –> development of secondary tumours

Question 20

What is hyperplasia?

Answer 20

The altered cell and its descendants grow and divide rapidly
- occurs in benign tumours

Question 21

What is dysplasia?

Answer 21

At some point one of these cells experiences another mutation that further increases its tendency to divide excessively and look abnormal
Presence of abnormal cells within a tissue or organ. Not cancer but might become cancer. Can be mild, moderate or severe.

Question 22

What is cancer in situ?

Answer 22

As time passes, one of the cells experiences yet another mutation causing a very abnormal structure, loss of differentiation and loss of contact between the cells. However it is still confined to the epithelial later from which is arose

Question 23

What is invasive cancer?

Answer 23

Additional mutations may occur after cancer in situ that enable it to invade neighbouring tissues and shed cells into the blood or the lymph.

Question 24

What do cancer cells look like under a microscope?

Answer 24

Large variably shaped nuclei
Many dividing cells
Disorganised arrangement
Variation in size and shape
Loss of normal features

Question 25

What is a proto-oncogene?

Answer 25

A gene involved in normal cell growth. Mutations in a proto-oncogene may cause it to become an ongogene which can cause the growth of cancer cells.
Specific part of DNA that controls cell division.
They drive the cell cycle forward, allowing cells to proceed from one cell cycle stage to the next.

Question 26

How can a proto-oncogene lead to cancer?

Answer 26

Different types of compounds can damage/ induce mutation in the part of DNA that is coding for a proto-oncogene can lead to cancer.

Question 27

What is an oncogene?

Answer 27

A mutated proto-oncogene which can cause cancer. It increases cell division and decreases cell differentiation and cell apoptosis (down-regulated).

Can occur from inherited mutations can be silent for some time of life, then with ageing the expression of the gene is more likely.

Question 28

What are tumour suppressor genes?

Answer 28

Genes in nucleus that code for proteins, e.g. p53, BRCA1/ Rad51.
Can do genetic testing to identify if a cancer gene carrier.

Mutation in BRCA1/ Rad51 can lead to breast or ovarian cancer.

Question 29

What is p53?

Answer 29

p53 is a transcription factor that responds to a number of cellular stresses including DNA damage.
It can induce apoptosis, cell repair and cellular senescence
It is a tumour suppressor gene

Damage to p53 gene has been identified in a number of cancers including sarcomas, leukaemias, brain tumours, adrenal tumours, breast cancer, lymphoma etc.

Question 30

What are telomeres?

Answer 30

Telomeres are repetitive DNA elements at the end of chromosomes
They protect the ends of chromosomes from degradation and from end to end fusion with other chromosomes

Question 31

What happens to telomeres during cell division?
Link to cancer?

Answer 31

The get shorter with division
Reaches a point where division can no longer occur leading to apoptosis
Telomerase maintains the lifespan of the chromosome from maintaining telomere length. This enzyme is not normally present/ active in normal cells.
In cancer cells, telomerase can be up-regulated and expressed to prevent telomere length reduction after divisions making the cells immortal.

Question 32

What lifestyle and environmental factor contribute to cancer development?

Answer 32

• Smoking
• Obesity
• Diet
• Alcohol
• Radiation
• Viral infections - increase risk of DNA mutations

Question 33

What causes cancer?

Answer 33

There is much debate as to whether environmental or genetic factors are the biggest contributors to cancer development. There are certain cancers that are more related to either genetics or environmental. e.g. pancreatic cancer is more related in inherited genetics than diet, however it is still a risk factor e.g. with alcoholism.

Currently the most prevalent cancers are linked to environmental factors.

Organs that have a quicker cell turnover are more at risk of developing cancer, e.g. colorectal cancer is more common in adults than bone. Has relationship to number of cell division.

Question 34

What are some treatements?

Answer 34

Surgery - to remove the tumour
Chemotherapy - utilisation of special drugs that are designed to target and kill cells that rapidly divide
Radiotherapy - highly advanced technology to deliver targeted beams of radiation to kill cancer
Immunotherapy - stimulate immune cells to recognise and destroy cancer cells

Question 35

How is oxidative stress related to cancer development?

Answer 35

Inflammatory conditions can increase oxidative stress which increase number of free radicals in the body. If balance of antioxidants and free radicals is not in a healthy range, this a risk factor to damage DNA and create mutations which can lead to cancer development.

Question 36

How is obesity related to cancer development?

Answer 36

Obesity means there is a large proportion of adipose tissue which can trigger an inflammatory pathway. High numbers of adipocytes can lead to inflammatory cytokine production which causes and inflammatory response. This increase oxidative stress in the body causing a larger production of free radicals. When there is more free radicals that antioxidants balanced in the body there is a greater risk of cancer development due to free radicals being able to cause damage to DNA which can then be mass replicated and become cancerous.

Question 37

What are some side effects of cancer treatments? RT & CT

Answer 37

• Loss of appetite
• Sore throat or mouth
• Dry mouth
• Dental and gum problems –> can alter oral micro-biome, can be linked to immune function
• Changes in taste or smell
• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Fatigue
• Depression
• Anaemia
• Infection risk

Question 38

What is immunotherapy?

Answer 38

Stimulation of immune cells to recognise and destroy cancer cells

Immune checkpoint inhibitors - block immune checkpoints, allowing immune cells to response more strongly to cancer
T-cell transfer therapy - boost natural ability of t-cells to fight cancer. Immune cells taken from tumour, the most active against cancer are selected or changed in the lab to better attack cancer cells, grown in larger batches, put back into the body through IV
Monoclonal antibodies - immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so they will be better seen and destroyed by the immune system
Immune system modulators - some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way

Question 39

What is T-cell therapy?

Answer 39

Form of immunotherapy
Boost natural ability of t-cells to fight cancer. Immune cells taken from tumour, the most active against cancer are selected or changed in the lab to better attack cancer cells, grown in larger batches, put back into the body through IV

Question 40

What are immune checkpoint inhibitors?

Answer 40

Form of immunotherapy
block immune checkpoints, allowing immune cells to response more strongly to cancer

Question 41

What are monoclonal antibodies?

Answer 41

A form of immunotherapy
Immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so they will be better seen and destroyed by the immune system

Question 42

What are immune system modulators?

Answer 42

Form of immunotherapy
Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way

Question 43

How is meat consumption linked to cancer?

Answer 43

Red meat has been seen to increase risk of colorectal cancer however it has been studied that it is more likely to be due to the consumption of HCAs (Heterocycline amines) and PAHs (Polycystic aromatic hydocarbons)

As red meat is high in haemoglobin, when cooked at high temperatures (e.g. BBQ) to the point where it becomes charred, which contains HCAs and PAHs. It is safe a low levels as the immune system is able to manage them. At high levels, or for those at risk of colorectal cancer, the consumption of HCAs and PAHS can lead to cancer development.

It is more down to the cooking method rather than the red meat itself. Lower risk with fish due to having less RBC and haemoglobin which is what forms HCAs

Question 44

What are HCAs and PAHs

Answer 44

Heterocyclic amines
Polycystic aromatic hydrocarbons

Produced when red meat is cooked at high temperature due to their RBC and haemoglobin content.
All food containing haemoglobin are at risk of forming HCA and PAH compounds.
Risk factors for production is type of food, cooking method, temperature and time.

Question 45

What are the risk factors for HCA developement?

Answer 45

Cooking method
Temperature
Type of food
Time cooked

Question 46

What dietary/storage factors can contribute to cancer development?

Answer 46

• Bisphenol from plastic food containers can increase risk of breast and prostate cancers (microplastic consumption –> immune response)
• HCA and PAH consumption from red meat being cooked at a high temperature and causing charring
• Food additives have been linked to risk of cancer development.

Question 47

How can cancer be prevented through diet?

Answer 47

Research has shown that a diet consisting of fruits, vegetables, spices and grains has the potential to prevent cancer.

Consumption of phtyochemicals
- Cartenoids
- Reservratrol
- Quercitin
- Curcumin
- Catechins
can decrease risk of cancer

Nitrite and nitrate is also linked to increasing the risk of cancer, however this is down to the source of nitrate. Nitrate from water and meat can increase risk of cancer, not the same with vegetables. Water is not allowed to contain more the 50mg nitrate due to the risk around cancer. Vegetables naturally contain phytochemicals and vitamin C which can reduce nitrate into other forms which reduce the risk of nitrate forming HCAs.

Large consumption of antioxidants from supplements was found to increase levels of oxidative stress so its found that the best way to consume antioxidants is through food. This is because it is consumed in combination with other compounds which can help amplify the physiological affect. When consumed in isolation the effect can be very different.

Question 48

How do phytochemicals help prevent cancer?

Answer 48

Protect against DNA damage
- Isothiocynates found in cruciferous veg eg. broccoli, inhibit tumourigensis by reducing genetic damage by a variety of chemical carcinogens.
- Similar phytochemicals in garlic and citrus fruits do the same

Effects on tumour cells
- Inhibit tumour growth by directly inducing cancer cell death by apoptosis
- Some pro-apoptotic activity has been found from curcumin from turmeric and resveratrol from grapes

Effects on angiogenesis
- Some phytochemicals have stron anti-angiogenetic properties which can have an effect on tumour cell growth
- Such as, Ellagic acid found in high quantities in raspberries and strawberries
- Delphinidin in blueberries
- EGCG in green tea

Question 49

What types of cancer does alcohol increase the risk of?

Answer 49

• Oral and digestive tract
• Liver
• Pancreas
• Breast

Heavy intake of alcohol (more than 50-70g per day) is a well established risk factor for liver and colorectal cancer

Question 50

How is alcohol consumption linked to cancer development?

Answer 50

Mechanism not fully understood
Studies indicate ethanol may be a ‘co-carcinogen’
The metabolism of ethanol to acetaldehyde generates free radicals which can then damage DNA and protein leading changes in cell proliferation.
Free radicals may also activate pro-carcinogens present in the alcoholic beverage causing production of carcinogens.

Question 51

What are carotenoids?
Where are they found?

Answer 51

Carotenoids found in fruit and vegetables have anti-carcinogenic activity.
Lycopene is one of the major carotenoids found in high concentrations in fruits such as watermelon, apricots, pink guava, grapefruit, rose hip and tomatoes.
The anticancer activity of lycopene has been confirmed in vitro and in vivo in animal models and humans

Question 52

What is resveratrol?
Where is it found?

Answer 52

A phytochemical that exhibits anticancer properties against a wide variety of cancers such as lymphoid, myeloid, myeloma, breast, prostate, stomach, colon, pancreas etc

The growth inhibitory effects are mediated through cell cycle arrest, repair or apoptosis pathways.

It is found in grapes, berries and peanuts

Question 53

What is quercitin?
Where is it found?

Answer 53

A phytochemical
One of the major dietary flavonoids found in fruits, vegetables, tea and wine.
Some studies have found when consumed from onions to reduce risk of lung cancer.
Shown to prevent colon and lung cancer in animal models

Question 54

What are catechins?
Where are they found?

Answer 54

Phytochemicals that have shown to have anticancer properties.
In patients with established premalignant conditions green tea derivatives have shown potential activity against cervical, prostate and liver malignancies without any major side effects.
Suggests a potential for prevention and treatment
Found in green and black tea

Question 55

What is curcumin?
Where is it found?

Answer 55

A phytochemical which in vitro studies have found it inhibits NF-kB and NF-kB regulated gene expression in a number of cancer cell lines
In vivo studies in animals and humans showed that curcumin inhibited carcinogenesis in breast, oesophageal, stomach and colon cancers.
Found in turmeric.

Question 56

How is vitamin C linked to cancer prevention?

Answer 56

Vitamin C is high in antioxidants which can protect against damage from free radicals.
World cancer research fund found that vitamin C reduces the risk of cancers of the stomach, mouth, pharynx, oesophagus, lung, pancreas and cervix.

Question 57

How are wholegrain food linked to cancer prevention?

Answer 57

Wholegrain food contain bioactive compounds such as vitamin E, tocotrienols, phenolic acids, lignins and phytic acid.
Refining grains reduces potential cancer preventative action of whole grains due to lack of bioactive compounds.

Other mechanisms of protection include:
- Influence of fibre on gastrointestinal cancers
- Fermentation of the fibre generates some short chain fatty acids such as butyrate which is known as a tumour suppressor
- Phytochemicals such as isoflavones in the wholegrains have chemoprotective actions against a number of cancers.