Genetic predisposition to cancer Flashcards
What is Cancer?
A common disease of somatic cells that are mostly due to chance and most are non-inheritable although increased chance with genetic predisposition
Oncogenes
1 mutation is sufficient for cancer and accelerates cell division
Protooncogene ==> Oncogene
Eg Thyroid cancer or by a virus
Tumour suppressor genes
1 mutation already in carrier eg BRCA1/2
Cells breaks which inhibit cell cycle and promote apoptosis
2 hit hypothesis
DNA damage response genes
Repair DNA and both genes fail = CANCER
Eg colon cancer
Base pair mismatch
Either have normal repair or defective repair (MMR+) which leads to MSI
Microsatellite instability
Addition of nucleotide repeats
Other causes of cancer include
Autosomal recessive syndrome
Multiple modifier genes which explains families with history but no mutation
De Novo Mutation
Mutation occurs newly in germ cell of parent
Most cancer susceptibility genes are…
Dominant with incomplete penetrance
Risks for breast cancer
Age, alcohol, diet, late menopause, no children, oestrogen use
BRCA 1
Checkpoint mediator for DNA damage signal and repair which remodels chromatin
Risks for colorectal cancer
Age, high fat, low fibre, IBS
How to manage cancer risk in Adenomatous polyposis syndrome
Surveillance, surgery, chemoprevention eg steroids
Predictive gene testing
Test relatives, surveillance, only test at adulthood and gene variant problems
Do polymorphisms cause disease?
NO - the wrong message does
