neoplasia: environment + genes

Question 1

carcinogenesis vs oncogenesis

Answer 1

carcinogenesis strictly applies to only malignant tumours.

oncogenesis is the causation of all tumours

Question 2

carcinogenesis

Answer 2

does not require continued presence of the causative agent.

Question 3

cancer + environment

Answer 3

85% of cancer is environmental

Question 4

host factors

Answer 4

race/ethnicity: customs + traditions

diet

constitutional factors: gender, inherited risks, age

premalignant lesions and conditions

transplacental exposure

Question 5

8 hallmarks of cancer

Answer 5

1. resisting cell death
2. sustaining proliferative signalling
3. avoid immune destruction
4. evading growth suppressors
5. enabling replicative immortality: most cells have finite number of times they can divide, cancer cells are immortal
6. tumour promoting inflammation
   inflammatory process promoted tumour formation
7. activating invasion and metastasis
   producing substances which allow it to invade into tissues
8. genomic instability: promoting mutations if the genome isnt being corrected

Question 6

cancer + DNA mutations

Answer 6

a single mutation does not cause cancer

a single mutation may change the risk of acquiring another mutation or developing cancer.

genes identified which can promote tumorigenesis i.e. driver genes.

Question 7

driver genes

Answer 7

signalling pathway regulating 3 core cellular processes:
cell fate
cell survival
genome maintenance

Question 8

types of mutations in basic gene types

Answer 8

1. proto oncogenes (cell proliferation)
2. tumour suppressor genes
3. apoptosis regulating genes
4. DNA repair genes

Question 9

proto oncogenes

Answer 9

are normal genes with normal function in a normal cell

their normal activity is to promote cell proliferation

examples:
growth factors
growth factor receptors
cell signal transducers
nuclear regulatory proteins and cell cycle regulators

mutated versions of these genes are called oncogenes.

Question 10

oncogenes single mutant alleles

Answer 10

sis, ras, c - myc

Question 11

tumour suppressor genes

Answer 11

normal function is to prevent uncontrolled growth:
gatekeeper genes
caretaker genes

gatekeeper genes inhibit proliferation and promote cell death

caretaker genes maintain the integrity of genome by DNA repair

usually both of the alleles need to be damaged for the mutation to occur

Question 12

knudson’s 2 hit hypothesis

Answer 12

both copies of the gene need to be damaged for the mutation to occur

Question 13

apoptosis regulating genes

Answer 13

shutting down cells that incur DNA damage

the family of genes responsible: Bcl - 2 protein with p53 component driving the process

normal p53: mutation detected and the cell is repaired or apoptosis induced

mutant p53: cell with mutation is not detected and the cell doesnt die but replicates

daughter cell will also carry p53 mutation

Question 14

DNA repair genes

Answer 14

DNA repair mechanisms required for:
replication errors
UV damage

mutations in DNA repair genes means that mutations wont be flagged