genetic predisposition to cancer

Question 1

Describe the basic mechanism of inherited predisposition to cancer & role of testing for sporadic mutation in oncology

Answer 1

Somatic tumour cells: Non-hereditary. Take place in non-germline tissues
Germ-line tumours: Hereditary. Take place in sperm cells and ovaries.
Hereditary predispositions:
-Oncogenes: Lead to uncontrolled cell division through transduction signalling and growth factors (autocrine and paracrine)
- Tumour suppressor genes: one inherited- can lead to development of bilateral retina-blastomas
-Dna repair genes:
-MRI: Mismatch repair genes- would usually repair base mutations in DNA.
CAN CAUSE:
MSI- micro satellite instability- add nucleotide sequences to DNA.
-recessive
-de novo mutations: occur in germ cells
Risk factors in cancer:
-age
-environment
-family history
-diet
-use of oestrogen

Question 2

Different risk factors associated with certain types of cancers

Answer 2

BREAST CANCER:
risk factors: ageing, oestrogen use, early/late menopause, lack of exercise, diet
hereditary: BRCA1- checkpoint metabolite, involved in DNA signalling and repair,
BRCA2- DNA repair by homologous recombination
CRC:
HNPCC- few adenomas. tumour seen throughout colon.
FAP- many adenomas, many secondary tumours, early onset, CHRPE
AFAP- upper GI lesions, few adenomas, late onset, no CHRPE
MAP- upper GI lesions, associated with MHY gene mutation
RETINOBLASTOMA:
two hit hypothesis
a. one mutation inherited, one developed: bilateral, secondary primaries
b. two mutations in same cell: untilateral, no secondary primaries