Food and Cancer -L9

Question 1

How many different types of cancers are there?

Answer 1

cancer is a collection of related diseases of about >200

Question 2

Why do most cancers start in epithelial cells ?

Answer 2

because this cell type divides more often

Question 3

What are the important aspects of cancer?

Answer 3

requires multiple mutations - within DNA
uncontrolled cell division as cells dont respond to stop signals
step-wise process
may damage surrounding organs- this is when tumours start being a problem
metastasis- causes serious problems

Question 4

define oncogenesis:

Answer 4

process of initiation of tumours in an organism

Question 5

define tumour:

Answer 5

tissue composed of cells that deviate from normal program of cell division and differentiation

Question 6

define benign tumour:

Answer 6

tumour cells remain in a single mass and do not invade or disrupt surrounding tissues

Question 7

define malignant tumour:

Answer 7

tumour cells invade and disrupt surrounding tissues

Question 8

define metastasis:

Answer 8

spread of malignant tumour cells throughout the body - normally through blood and lymphatic system

Question 9

What does it mean by cancer cells are defined by their origin ?

Answer 9

they will act like the cell type from their origin wherever they appear
e.g. breast cancer cells act like breast cancer cells wherever they are

Question 10

What pathway can lead to cancer ?

Answer 10

1) mutation inactivates TSG
2) cell proliferates
3) mutations inactivates DNA repair gene
4) mutation of proto-oncogene creates an oncogene
5) mutation inactivates several more TSG
6) CANCER

Question 11

What mutations most commonly occur in cancers?

Answer 11

most cancers result from mutations in cellular genes
other cancers are caused by viruses - viruses can insert their DNA into our DNA
- mutations occur in genes involved in cell division

Question 12

What are cancers of epithelial cells, bones and muscle cells?

Answer 12

epithelial= carcinomas

bone and muscle= sarcomas

Question 13

How much of cancers are sporadic ?

Answer 13

90-95%

- only a small proportion are genetically related

Question 14

What does cell differentiation correlate with ?

Answer 14

loss of ability to proliferate - highly specialised cells are terminally differentiated

Question 15

What is required for a cell to undergo differentiation ?

Answer 15

it has to divide and during this it alters itself, altering the proteins it is going to produce
but once a cell is terminally differentiated then it will no longer divide because it is highly specialised - they are replaced by new cells

Question 16

What signalling molecules control normal cell cycle ?

Answer 16

growth factors- stimulate cell division

growth-inhibiting factors- inhibit cell division

Question 17

What signals are cancer cells unable to respond to ?

Answer 17

unable to respond normally to intra-cellular and/or extracellular signals that control cell proliferation, differentiation and ultimately cell death

Question 18

What are the frequency of genetic mutations that can occur in different types of cancer ?

Answer 18

can be as few as 2 to at least 6 mutations - likely that more occur during the disease to increase malignancy

Question 19

Why do not all mutations lead to cancer?

Answer 19

sometimes mutations can be fixed, may not cause a change, some are beneficial (evolution), majority of DNA is not involved in cell division

Question 20

What are the 6 stages of cancer progression ?

Answer 20

1) loss of growth signal automomy
2) evasion of growth inhibitory signals
3) evasion of apoptosis
4) unlimited replicative potential
5) angiogenesis- tumours develop blood supply which is a key part to tumours being successful
6) invasion and metastasis

Question 21

According to the IARC how many factors are there that are carcinogenic to humans ?

Answer 21

116

• many are related to occupation
• many are unavoidable

Question 22

Not all mutations will lead to cancer because…

Answer 22

• mutation is repaired
• mutation is not repaired but it is not in a “bad” place
• mutation is in a bad place is not recognised but is dealt with and recognised by defines systems

Question 23

How many mutations occur in our DNA everyday ?

Answer 23

10,000 mutations per day in human
1 in 1000 in these changes survives because they are repaired by one of a number of different DNA repair enzymes - these are critical

Question 24

What would a a really bad thing associated with DNA repair systems?

Answer 24

if they suffered mutations and their efficiency was reduced- defects or inefficiencies of the DNA repair system will increase the number of mutations increasing the likelihood of cancer

HOWEVER stimulating their efficiency would be a good thing

Question 25

What is one of the most common inherited cancer syndromes?

Answer 25

hereditary non-polyposis colon cancer results from defects in mis-match repair- with at least 5 different mismatch repair genes involved - it develops at an early ages

Question 26

What 3 types of genes are frequently mutated in cancer?

Answer 26

1) proto-oncogenes to oncogenes 2) Tumour suppressor genes 3) genes linked to mutation rate- any gene that increases mutations occurring

Question 27

How many different oncogenes have been discovered and what is their purpose?

Answer 27

about 100 different oncogenes | all proto-oncogenes are involved in positive control of cell growth and division

Question 28

What are the 2 classes of proto-oncogenes?

Answer 28

growth factors= regulatory genes involved in the control of cell multiplication protein kinases= add phosphate groups to target proteins, important in signal transduction pathways

Question 29

How were oncogenes originally discovered?

Answer 29

discovered in tumour-causing viruses but then found to be similar to or derived from genes present in animal host cells called proto-oncogenes

Question 30

What are oncogenic mutations like ?

Answer 30

mutations that produce oncogenes are genetically dominant oncogenic defect can be in any of the proteins in communicating the "divide" signal e.g. growth factors, transmembrane proteins, cytoplasmic proteins, nuclear transcription factors

Question 31

What is Ras and what is the issue with it ?

Answer 31

it is a mutant form of a G protein which is common in tumour cells - ras oncogene is always active and encodes a protein with normal GTP binding but not GTPase activity and therefore this is why it is always active - this means unregulated growth

Question 32

What % of lung, colon and pancreatic cancer are associated with ras mutations ?

Answer 32

30-50% lung and colon | 90% pancreatic

Question 33

What do defects in TSGs cause?

Answer 33

removes the normal restraints on cell division defects in one or more TSGs can lead to tumour formation mutations in TSGs are genetically recessive - therefore if you inherit one correct copy and one defective copy you won't be diseased

Question 34

How many cancers have mutations in p53 gene?

Answer 34

half of all known cancers

Question 35

What is p53?

Answer 35

it is a transcription factor with greater than 100 different target genes mutations lead to increase half life

Question 36

How does unregulated growth occur ?

Answer 36

-gain of function mutations of proto-oncogenes producing an oncogene -loss of function mutations in TSGs LOF are more common but both alleles must be involved as it is genetically recessive

Question 37

What are the stages of colorectal cancer ?

Answer 37

1) normal colorectal epithelium - altered by a TSG 2) early adenoma- oncogene produced 3) intermediate adenoma- maybe another TSG mutated 4) advanced adenoma- p53 mutation 5) colorectal carcinoma 6) invasive carcinoma 7) metastatic carcinoma Numerous different mutations at each stage - the effects of mutations are not all or none

Question 38

What are the GOF mutations identified in colon cancer and what function do they affect?

Answer 38

K-ras | - alters signal transduction

Question 39

What are the LOF mutations identified in colon cancer and what function do they affect?

Answer 39

``` APC - alter cell adhesion SMAD (DCC) - alter proliferation and differentiation p53 - alter DNA repair and apoptosis MSH2and MLH1 - alter DNA repair ```

Question 40

Why is apoptosis so important in cancer and tumour formation ?

Answer 40

because for a tumour to be successful it needs to have inactivated apoptotic processes both the intrinsic and extrinsic pathways can have alterations in them - many have inactivated the p53 pathway REACTIVATING this apoptic pathway is a key research area

Question 41

What are telomeres?

Answer 41

repeated sequences of DNA that protect the ends of chromosomes

Question 42

What is the end replication problem ?

Answer 42

it causes DNA damage and activates p53

Question 43

How is senescence induced?

Answer 43

induced by telomere shortening

Question 44

What does the inactivation of p53 cause?

Answer 44

it forces the cell to enter crisis instead of senescence

Question 45

How do cancer cells evade crisis?

Answer 45

immortal cells can escape crisis by activating hTERT- this is activated in >90% of cancers