Genetic Predisposition to Cancer Flashcards
Mutations cause faulty proteins, what are the possibilities?
- Functional protein
- Non-functional or missing protein
- Protein with reduced function
What does cancer arise from?
Gene mutations
Describe the cell cycle?
What are oncogenes?
Oncogenes = regulate cell growth
- A mutation of oncogenes leads to accelerated cell division, and ultimately maybe cancer
What are tumour suppresor genes?
Tumour suppressor genes = normal genes that slow down cell division, repair DNA mistakes or tell cells when to die
- 1st mutation makes you susceptible to cancer
- 2nd mutation leads to cancer
Describe the pathogenesis of cancer, using colon cancer as an example?
What is the main mechanism for familial cancer?
Faulty DNA mismatch repair
Is familial cancer autosomal dominant or recessive?
Is autosomal dominant inheritance:
- Each child has 50% chance of inheriting mutation
- No skipped generations
- Equally transmitted by men and woman
What is Lynch syndrome/HNPCC?
Is a mutation in mismatch repair genes:
- Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancer
- Adenoma-carcinoma sequence for polyp formation
What cancers does Lynch syndrome/HNPCC increase risks of?
Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancer
What are clinical features of lynch syndrome/HNPCC?
- Early but variable age of diagnosis
- Tumour site in proximal colon predominates
What investigations are done for lynch syndrome/HNPCC?
- Genetic testing
- IHC for mismatch repair gene proteins
- Or microsatellite instability testing (MSI)
What is Lynch syndrome also known as?
Hereditary non-polyposis colorectal cancer (HNPCC)
When should you suspect hereditary cancer syndrome?
- Cancer in 2 or more close relatives
- Early age of diagnosis
- Multiple primary tumours
- Bilateral or multiple rare cancers
Describe the cancer genetics process at the clinic?
- Detailed family history
- Verbally reported pedigree and then revised pedigree based on pathology reports
- Confirm diagnosis of cancer
- Risk estimation
- Genetic centres can classify people as gene carrier who is high, medium or low risk (low risk being similar to population average)
- Interventions
- Awareness of symptoms/signs
- Lifestyle – diet, smoking, exercised
- Prevention – oestrogen, aspirin
- Screening
- Prophylactic surgery
- Genetic testing
- Consider in high risk
What interventions can be done for people with increased risk of cancer?
- Awareness of symptoms/signs
- Lifestyle – diet, smoking, exercised
- Prevention – oestrogen, aspirin
- Screening
- Prophylactic surgery
What are the benefits and risks of genetic testing?
What cancers are associated with BRCA1/2 mutations?
- Breast cancers 60-80%
- Second primary breast cancer 40-60%
- Ovarian cancer 20-150%
- In males, increased risk of prostate and breast cancer
What are options for breast cancer surveillance?
- Breast awareness
- Early clinical surveillance
- Annual clinical breast exams
- Mammography
- Indications – moderate/high risk
- 2 yearly from 35-40 then yearly from 40-50
- MR
- Indications – those at highest risk
How often do people with BRCA1/2 mutations get a mammograph?
- 2 yearly from 35-40 then yearly from 40-50
Describe the management of BRCA1/2 mutations?
- Prophylactic mastectomy
- Removes most but not all breast tissue
- Massively reduces risk
- Total mastectomy removes more breast than subcutaneous mastectomy
- Prophylactic oophorectomy
- Eliminates risk of ovarian cancer
- Complications – surgical menopause
What is done for colorectal cancer surveillance for those at risk due to gene mutations?
Colonoscopy:
- 2 yearly from ages 25 to 35 if gene carrier
- 5 yearly from 50 if moderate risk
Who are 1st, 2nd and 3rd degree relatives?
