What do most cancers arise from
Genetic mutations either sporadic or inherited
What kind of cancer mutation is non inheritable
somatic
What causes germ-line mutations
Hereditary -present in egg or sperm of parents
What are tumours
clonal expansions
What are the three genetic processes associated with cancer syndromes
Oncogenes
Tumour suppressor genes
DNA damage-response genes
What are oncogenes
Mutated proto-oncogens that accelerate cell division
How many mutations are needed to active oncogenes
1
What is the role tumour suppressor genes
Inhibit cell growth
promote apoptosis
Cells breaks
When does cancer arrive with tumour suppressor genes
when both tumour suppressor genes fail
Where does the two hit in tumour suppressor genes occur resulting from carrier to cancer
first - germ line (carrier)
second - tumour formation
What do DNA damage-response genes do
The repair mechanics for DNA
When does cancer arrive from DNA damage-response genes
both genes fail, speeding the accumulation of mutations in other critical genes
Give an example of a DNA damage response gene MMR
failure to mismatch due to single base mismatches or short insertions and deletions leads to accumulation of nucleotide repeats - Microsatellite instability
What is the evidence that DNA damage response genes aren’t working
Microsatellite instability
What is de novo mutations
mutations occurring in there germ line of parents with no family history of hereditary cancer
How do we look for inherited cancers
family history
What are most cancer susceptible genes
autosomal dominant with incomplete penetrance - therefore have genes but do not show the symptoms
What is sporadic cancer
cancer by chance
If tumours are heritable they are usually bilateral with increases the risk of what and why
secondary primer
because every cell carries the mutation
How is Retinoblastoma cancer occur
due to heritable or non heritable tumour supressor genes
What are the risks factors for breast cancer
Ageing Family history Hormones - late menopause/pill/HRT Dietary factors Lack of exercise
What is the most likely and second most likely gene to causes breast cancer and by what mutation
BRCA 1 then BRCA2
spordic
What is BRCA1 genes functions
Checkpoint mediator DNA damage signalling and repair Chromatin remodelling (inactive Xchromosome)
What is BRCA2s functions
DNA repair by HR (homologous recombination)
What else can BRCA1/2genes cause
Secondary breast cancer
Ovarian cancer
Male breast cancer
What cancer conditions can arise from tumour suppressor gene
Breast cancer
ovarian cancer
Retinoblastoma
What are the risk factors for colorectal cancer
Ageing Personal history of CRC or adenomas High-fat, low-fibre diet Inflammatory bowel disease Family history of CRC
How does Hereditary nonpolyposis colorectal cancer occur
DNA Mismatch Repair of HNPCC gene
what does polyposis and non polyposis mean
multiple adenomas present
No adenomas - but there is a risk of development
Lynch syndrome aka HNPCC is what
autosomal dominant genetic condition that has a high risk of colon cancer
What gene causes severe polyposis in colon cancer
FAP - familial adenomatous polyposis
What is clinical features of HNPCC
Tumor site throughout colon rather than descending colon
Extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors
Clinical Features of FAP
Estimated penetrance for adenomas >90%
Risk of extracolonic tumors
Untreated polyposis leads to 100% risk of cancer
What is autosomal recessive cancer syndrome and example
need to Inherit copies in both parents to show symptoms e.g. MYH polyposis
What explains a family with history of cancer but no identified mutation
Multiple modifier genes of lower genetic risk
How are cancer risk in Adenomatous Polyposis syndromes treated
Surveillance
Surgery
Chemoprevention
