13. How And Why Neoplasms Occur

Question 1

What factors account for cancer risk?

Answer 1

Intrinsic - eg heredity, age and gender (especially hormonal.
Extrinsic - eg environment and behaviour.

Question 2

What are the 5 leading behavioural and dietary risks that account for 30% of cancer deaths?

Answer 2

High BMI.
Low fruit and vegetable intake.
Lack of physical activity.
Tobacco use.
Alcohol use.

Question 3

What accounts for 85% of a populations cancer risk?

Answer 3

Extrinsic factors (chemicals, radiation, infection).

Question 4

How much time is there between carcinogen exposure and malignant neoplasm onset?

Answer 4

Long delay

Question 5

What is the relationship between risk of cancer and carcinogen dosage?

Answer 5

Risk of cancer depends on total carcinogen dosage

Question 6

True or false, there is no organ specificity for particular carcinogens?

Answer 6

False, there is sometimes organ specificity for particular organs

Question 7

Why do industrial carcinogens have an effect primarily on the relevant workers and the effect of tobacco smoke is largely limited to smokers?

Answer 7

The risk of cancer’s dependence on dosage.

Question 8

Give 3 classifications of mutagenic chemical carcinogens

Answer 8

Polycyclic aromatic hydrocarbons.
Aromatic amines.
N-nitroso compounds.
Alkylating agents.
Diverse natural products eg aflatoxin, asbestos.

Question 9

What are pro-carcinogens?

Answer 9

Chemicals that are only converted to carcinogens by the cytochrome P450 enzymes in the liver.

Question 10

What are complete carcinogens?

Answer 10

Carcinogens that act as both initiators and promotors.

Question 11

What is radiation?

Answer 11

Any type of energy travelling though space

Question 12

What does ultraviolet light penetrate?

Answer 12

No deeper than skin

Question 13

What does ionising radiation do in the body to atoms? Give 2 examples

Answer 13

Strips electrons from atoms.

X-rays and nuclear radiator arising from radioactive elements (alpha particles, beta particles, gamma rays).

Question 14

How does radiation damage DNA?

Answer 14

Directly and indirectly by generating free radicals.

Question 15

What in the DNA is damaged by ionising radiation?

Answer 15

DNA bases, and causes single and double strand DNA breaks

Question 16

In what 2 ways can carcinogenic infections act on cells?

Answer 16

Directly affect cell growth by affecting genes that control cell growth.
Indirectly affect cell growth by causing chronic tissue injury where the resulting regeneration acts either as a promotor for any pre-existing mutations, or else causes new mutations from DNA replication errors.

Question 17

How does HPV act as a direct carcinogen to cause cervical carcinoma?

Answer 17

Expresses the E6 and E7 proteins that inhibit p53 and pRB protein function respectively, both of which are important in cell proliferation (control the cell cycle).

Question 18

Give an example of a virus that are indirect carcinogens causing chronic liver cell injury and regeneration

Answer 18

Hepatitis B and C

Question 19

How does Helicobacter pylori increase the risk for gastric carcinomas?

Answer 19

Causes chronic gastric inflammation

Question 20

How does HIV lead to an increased neoplasm risk?

Answer 20

Acts indirectly by lowering immunity, allowing other potentially carcinogenic infections to occur

Question 21

What is the two hit hypothesis?

Answer 21

Need both alleles of a gene to mutate to cause a neoplasm. Therefore in familial cancers, first hit is delivered through the germline and effects all the cells in the body. The second hit is a somatic mutation. As only one mutation is needed, neoplasm can develop quicker.

Question 22

What are tumour suppressor genes?

Answer 22

Inhibit neoplastic growth.

Question 23

What are proto-oncogenes?

Answer 23

When activated, enhance neoplastic growth

Question 24

Do tumour suppressor genes and proto-oncogenes need 1 or 2 hits to allow a neoplasm to grow and why?

Answer 24

Tumour suppressor genes - both alleles much be inactivated, as inhibit neoplastic growth, so even with just one normal allele they can still do that.
Proto-oncogenes - one allele, as once activated it enhances neoplastic growth.

Question 25

What oncogene is mutated in approximately a third of all malignant neoplasms?

Answer 25

RAS

Question 26

What does the RAS proto-oncogene encode? So what does it encode when mutated?

Answer 26

A small G protein that relays signals into the cell that eventually pushes the cell past the cell cycle restriction point.
Mutant RAS encodes a protein that is always active, producing a constant signal to pass through the cell cycles restriction point.

Question 27

Give 2 examples of genes that proto-oncogenes encode

Answer 27

Growth factor receptors eg HER2.

Transcription factors eg MYC.

Question 28

What causes xeroderma pigmentosum?

Answer 28

Autosomal recessive condition due to mutations on a DNA repair gene that affects DNA nucleotide excision repair.

Question 29

What 3 types of genes can cause neoplasms when mutated?

Answer 29

Tumour suppressor genes.
Proto-oncogenes.
DNA repair genes.

Question 30

What are patients with xeroderma pigmentosum experience?

Answer 30

Very sensitive to UV damage and develop skin cancer at a young age.

Question 31

What type of inheritance is hereditary non-polyposis colon cancer syndrome, what genes does it affect and what cancer is it associated with?

Answer 31

Autosomal dominant.
Affects a DNA mismatch repair gene.
Colon cancer.

Question 32

What genes are associated with familial breast carcinoma and what are they important for?

Answer 32

BRCA1 and BRCA2.

Repair double strand DNA breaks.

Question 33

What is genetic instability?

Answer 33

Accelerated mutation rate found in malignant neoplasms due to abnormal chromosome segregation.

Question 34

What are caretaker genes?

Answer 34

Tumour suppressor genes that maintain genetic stability.

Question 35

How many mutations are needed to make malignant neoplasm, and of what genes?

Answer 35

Multiple mutations of a combination of tumour suppressor genes and proto-oncogenes.

Question 36

What is cancer progression?

Answer 36

Progression from normal epithelium, to adenoma, to carcinoma, with the accumulation of mutations over decades.

Question 37

What are the 6 hallmarks of cancer that a fully evolved malignant neoplasm exhibits?

Answer 37

Self-sufficiency in growth signals.
Resistance to growth stop signals.
No limit on the number of times a cell can divide.
Sustained ability to induce new blood vessels.
Resistance to apoptosis. (This and all above related to growth, so are relevant to both benign and malignant neoplasms).
Ability to invade and produce metastases. (Only malignant tumours).
(Plus genetic instability as an enabling characteristic).