genetic predisposition to cancer Flashcards
cancer arises from …
gene mutations
somatic/germline
somatic mutation
occur in non-germline tissues, non inheritable
germline mutations
mutation in gametes, all cells affected in offspring, heritable and cause family cancer syndromes
genetic processes associated with cancer
oncogenes
tumour suppressor genes
DNA damage response genes
mismatch repair genes
oncogenes
proto-oncogenes: normal gene that codes for proteins to regulate cell growth and differentiation
mutations can change a proto-oncogene into an oncogene
oncogenes accelerate cell division
1 mutation is sufficient for role in cancer development
tumour suppressor genes
cell’s brakes for cell growth
genes inhibit cell cycle/promote apoptosis or both
cancer arises when both brakes fail (2 hit hypothesis) - 1st mutation: susceptible carrier, 2nd mutation: leads to cancer
DNA damage response genes
repair mechanics for DNA
Cancer arises when both genes fail, speeding the accumulation of mutations in other critical genes
mismatch repair genes
MMR corrects errors that spontaneously occur during DNA replications
HNPCC results from failure of mismatch repair genes
Mismatch repair failure leads to micro-satellite instability - MSI is the phenotypic evidence that MMR is functioning abnormally, these cells tend to accumulate errors
benign vs malignant
benign - lacks ability to metastasise, rarely/never become cancerous, can still cause -ve health effects
dysplastic: benign but could progress to malignancy, cells show abnormalities in appearance and cell maturation - sometimes referred to as premalignant
malignant: not benign, able to metastasise
dominantly inherited cancer syndromes
oncogene: MEN2 and familial medullary thyroid cancer; RET gene
tumour suppressor gene: breast/ovarian cancer, FAP, Li-Fraumeni syndrome, retinoblastoma; BRCA1/2, APC, P53, RB
DNA repair: HNPCC/Lynch syndrome; MLH1, MSH2/6, PMS1/2
Other causes of cancer
autosomal recessive syndromes
multiple modifier genes of lower genetic risk
de novo mutations
new mutation occurs in germ cell of parent
no family history of hereditary cancer syndrome
common in: FAP, multiple endocrine neoplasia, hereditary retinoblastoma 2B
what does FAP stand for
familial adenomatous polyposis
most cancer susceptibility genes are …
dominant with incomplete penetrance
retinoblastoma
1/20 000 children
most common eye tumour in children
occurs in hereditable and non-hereditable forms
identifying at risk infants reduces morbidity and mortality