Genetics - Predisposition to cancer Flashcards
What is an oncogene?
Role of tumor suppressor genes?
Mutation in these genes leads to out of control growth in the cell - they stop genes deemed for apoptosis so they can survive.
Normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death).
What is a germline mutation?
What is a somatic mutation?
Germline: if parent has a child, the child will have an alteration in every cell in their body - these are heritable, causes cancer family syndromes.
Somatic: Mutation arrising in one cell, doesn’t effect germ line
Please explain DNA mismatch repair.
- Classically seen in lynch syndrome
- DNA is copied, very occasionally a mistake arrises: normally body’s repair protein sorts out but if not correct then there is an additional base on the protein: causing a nonsence mutation = non-functioning protein
What is extragenic DNA?
DNA that has no role in coding: chunks of DNA that is in between DNA which codes for specific things.
What occurs to non-functional or missing protein?
Nonsence mediated decay with premature stop codons - person ends up with half as much protein that they should have.
How much breast and ovarian cancer is hereditary?
1/8 women get breast cancer
1/70 get ovarian cancer
Breast cancer: 5-10% hereditary, 15-20% family clusters
Ovarian cancer: 5-10% hereditary
What are the genes for breast cancer?
- BRCA 1
- BRCA 2
- p53
Colorectal cancer susceptibility: which genes are responsible?
- Familial: 10-30%
- HNPCC (hereditary nonpolyposis colorectal cancer) aka Lynch syndrome: 5%
- FAP (familial adenomatous polyposis): 1%
A child presents with a white pupil on flash photography: what needs to be remembered?
Notice the white pupil, leukochoria: seeing through the pupil a tumour that has arisen in the retina. If the child has a germline mutation then they have a high risk of tumour in their other eye – clinical emergency.
- this is retinoblastoma
Explain Lynch syndrome:
How can lynch syndrome be prevented?
- Mutation in mismatch repair genes
- Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers
- Adenoma- carcinoma sequence for polyp formation
- Great opportunity for prevention by colonoscopy
What are the clinical features of lynch syndrome?
- Early but variable age at CRC diagnosis (~45 years)
- Tumor site in proximal colon predominates
What is the lifetime risk of BRCA1 and 2?
- Breast cancer: 60-80%
- Second primary breast cancer: 40-60% [prophylactic mastectomy]
- Ovarian cancer 20-50%
- Males have an increased risk of prostate cancer and breast cancer
What is the chance of inheriting risk in autosomal dominant inheritance?
- Each child has 50% chance of inheriting the mutation
- No “skipped generations”
- Equally transmitted by men and women
What is the mendelian risk?
50% risk of carrying mutation,
can only be given when a clear basis of single gene inheritance can be recognized for disorder
When do we suspect hereditary cancer?
- Cancer in 2 or more close relatives (on same side of family)
- Early age at diagnosis
- Multiple primary tumors
- Bilateral or multiple rare cancers
- Characteristic pattern of tumours (e.g. breast and ovary)
- Evidence of autosomal dominant transmission
