familial cancer

Question 1

what properties must cells acquire to become malignant

Answer 1

•	Uncontrolled cell division 
•	Loss of cell adhesion 
•	Loss of regulation 
•	Proliferative signalling - stimulation to tell the cell to keep avoiding 
•	Avoidance of apoptosis 
•	Bypassing replicative senesce 
Insensitive to anti-growth signalling

Question 2

Tumour suppressor genes

Answer 2

These are cancer genes that when altered, tend to result in a loss of protein function. They usually require loss of the wild-type allele.
When functioning normally they may:
• Negatively regulate cell-cycle progression
• Couple DNA damage recognition to cell-cycle control
• Promote apoptosis
• Play a role in cell adhesion

Question 3

what are proto-oncogenes

Answer 3

Normally stabilise the cell cycle and are involved in growth and repair of the tissues. Activation leads to oncogenes with gain of function – become over-active. One faulty copy is usually enough to give a tumour effect.

Question 4

what are the two main cancer types

Answer 4

sporadiac (common) and familial (uncommon)

Question 5

which features would indicate familial cancer both at a individual level and in the family history

Answer 5

individual - lots of primary tumours, early age of onset
FMH - More than one individual in the same family affected by similar cancers or cancers at related sites with early age of onset

Question 6

which cancers are associated with familial breast cancer

Answer 6

ovarian and male breast cancer

Question 7

which two genes are most associated with familial breast cancer

Answer 7

BRCA 1 and 2

Question 8

define penetrance

Answer 8

risk of developing the disease if you have the variant. The proportion of individuals with a particular genotype who develop the phenotype.

Question 9

what it the normal function of the BRCA genes

Answer 9

DNA repair by homologous recombination of double-stranded breaks

Question 10

what causes hereditary non-polyposis colon cancer (HNPCC)

Answer 10

Inherited mutations in MMR system. Mis-match repair system is important for accurate DNA replication. It fixes when a single nucleotide has been inserted in the wrong place

Question 11

where else can cancer arise in HNPCC apart from the colon

Answer 11

uterus, stomach, ovary

Question 12

how is HNPCC screened for

Answer 12

regular colonoscopies. Frequency determined by risk: • 2 yearly colonoscopies from the age of 25
• 2 yearly upper GI endoscopy from the age of 50 – also at risk of developing gastric cancer

Question 13

which genes are implicated in HNPCC

Answer 13

	MLH1 – 50%
	MSH2 – 40% 
	MSH6 – 7-10%
	PMS2 - <5%
	Each of these genes produce proteins which form part of the molecular complex repairing mis-matched DNA

Question 14

what is FAP

Answer 14

familial adenomatous polyposis.
o Numerous polyps form. Start out benign but if left untreated become cancerous
Patients require annual bowel screening from the age of 11.
Can develop congenital hypertrophy of the retinal pigmented epithelium - see black spots in their eyes which can indicate they have the condition

Question 15

what causes FAP

Answer 15

APC gene defects results in tumour suppressor gene flaws