genetic predisposition to cancer Flashcards
what two types of gene mutations are there relating to cancer?
somatic and germline
what type of mutation causes cancer family syndromes?
germline
where are germline mutations present?
egg or sperm cells
what is a proto-oncogene?
normal gene that codes for proteins to regulate cell growth and differentiation
what is the effect of oncogenes?
accelerated cell division
what can change a proto oncogene into an oncogene?
mutation
how many mutations are sufficient for oncogenes to play a role in cancer development?
1
what are tumour suppressor genes?
cells “brakes” for cell growth
what are the effects of tumour suppression genes?
inhibit cell cycle
promote apoptosis
how many mutations must occur for tumour suppression genes to play a role in cancer development?
2
what do DNA damage-response genes do?
repair DNA
how many DNA damage response genes have to fail to cause cancer?
when both genes fail
what does mismatch repair failure lead to?
microsatellite instability
what is the effect of MMR?
corrects errors that spontaneously occur durinf DNA replication like single base mismatches or short insertions and deletions
what are created as a result of defective MMR?
novel microsatellites fragments called simple sequence repeats
what characterises a benign tumour?
tumour lacks the ability to metastasize
what characterises a dysplastic tumour?
benign tumour that has the potential to progress to malignancy
what would you see histologically in a dysplastic tumour?
abnormal cell appearance and cell maturation
what characterises a malignant tumour?
able to metastasize
what is a de novo mutation?
new mutation that occurs in germ cell of a patient
what is a retinoblastoma?
most common eye tumour in children
what is the difference between nonheritable and heritable retinoblastoma?
unilateral in nonheritable
usually bilateral in heritable
increased risk of second primary cancers in heritable
family history in around 20% of cases in heritable
heritable cancers typically present at a younger age
what are some risk factors for breast cancer?
ageing family history dietary factors lack of exercise estrogen use
what is the most common known gene that contributes to the development of breast cancer?
BRCA1
what are some functions of BRCA1
checkpoint mediator
DNA damage signalling and repair
chromatin remodelling
transcription
what are some functions of BRCA2?
DNA repair by homologous recombination
what is the risk of developing a BRCA1 associated cancer?
Breast - 50-85%
second primary breast cancer - 40-60%
ovarian cancer - 15-45%
what is the risk of developing a BRCA2 associated cancer?
breast cancer: 50-85%
male breast cancer: 6%
ovarian cancer: 10-20%
what are some risk factors for colorectal cancer?
ageing personal history high fat low fibre diet IBS family history of CRC
what are some hereditary colorectal cancer syndromes?
non-polyposis
polyposis
what is an example of a non-polyposis CRC syndrome?
hereditary non-polyposis colon cancer- HNPCC
what are some example of polyposis CRC syndromes?
FAP - severe colonic polyposis
AFAP - less severe colonic polyposis
MAP - varying degrees of colonic polyposiss
what does FAP stand for?
familial adenomatous polyposis
what are some clinical features of HNPCC?
tumour site throughout colon rather than descending colon
can lead to the development of extracolonic cancers (endometrium, ovary)
what are some clinical features of FAP?
over 90% penetrance for adenomas
risk of extracolonic tumours
CHRPE
untreated polyposis leads to 100% risk of cancer
what does CHRPE stand for?
congenital hypertrophy of the retinal pigment epithelium
what are some clinical features of AFAP?
later onset few colonic adenomas not associated with CHRPE upper GI lesions associated with mutations at the 5' and 3' ends of APC gene
what can oppose the effect of inherited cancer genes?
multiple modifier genes of lower gentic risk
how are adenomatous polyposis syndromes managed?
surveillance
surgery
chemoprevention
are the majority of cancers sporadic or inherited?
sporadic
what is the effect of an inherited mutation?
increased PREDISPOSITION to cancer
