Genetics: predisposition to cancer Flashcards
How much of breast and ovarian cancer is hereditory?
○ Breast cancer - 1 in 8 people get breast cancer - 5-10% hereditary - 15-20% family clusters ○ Ovarian cancer - 1 in 70 people get ovarian cancer - 5-10% hereditary
How might cancers arise from gene mutations?
○ Germline mutation - Present in egg or sperm - Are heritable - Cause cancer family syndromes ○ Somatic mutation - Occur in non-germline tissues - Are nonheritable
What are oncogenes and how do mutations effect them?
○ Regulate cell growth (stopped car)
○ 1st mutation leads to accelerated cell division (press on accelerator of the car and run into a wall)
○ 1 mutation is sufficient for role in cancer development
What are tumour suppresser genes and how do gene mutations effect them?
○ Normal genes- prevent cancer (normal car that can break before the wall)
○ 1st mutation- susceptible to cancer (break for the back wheels of the car don’t work and so might hit the wall)
○ 2nd mutation- leads to cancer (no breaks work and so the car will hit the wall)
What is hereditory non-polyposis colorectal cancer/ lynch syndrome?
○ Mutation in mismatch repair genes
○ Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers
○ Adenoma- carcinoma sequence for polyp formation
What are the clinical features of hereditory non-polyposis colorectal cancer/ lynch syndrome?
- Early but variable age at CRC diagnosis (~45 years)
- Tumour site in proximal colon predominates
When should you suspect hereditary cancer syndrome?
○ Cancer in 2 or more close relatives (on same side of family)
○ Early age at diagnosis
○ Multiple primary tumours
○ Bilateral or multiple rare cancers
○ Characteristic pattern of tumours (e.g. breast and ovary)
○ Evidence of autosomal dominant transmission
What are the guidelines for risk estimation?
○ All Scottish genetics centres ○ Similar to UK National Guidelines ○ Recommended use by all doctors ○ Screening has support of Scottish Government ○ Classify as high, moderate or low ○ Low is low genetic risk - similar to population average risk
What happens in a clinical genetics consultation?
○ Go through family history
○ Risk estimation
○ Explanation of basis of risk
○ Interventions
- increased awareness of symptoms / signs
- lifestyle: diet, smoking, oestrogen use
- screening
- prophylactic surgery
○ Genetic testing - consider in high risk
What are the breast cancer survaliance options?
○ Breast awareness
○ Early clinical surveillance 5 year
What happens in prophylactic vasectomy?
- Removes most but not all breast tissue
- Significantly reduces breast cancer risk in women with a family history
- Total (simple) mastectomy removes more breast tissue than subcutaneous mastectomy
- BRCA1 mutation-positive women breast cancer incidence reduced to 5%
What happens in a prophylactic oopherectomy?
○ Eliminates risk of primary ovarian cancer; however, peritoneal carcinomatosis may still occur
○ Laparoscopic oophorectomy reduces postsurgical morbidity
○ Induces surgical menopause but HRT till 50 does not change BRCA risk
○ Risk of subsequent BRCA halved in mutation-positive women
What is the survalience for CRC?
○ Colorectal cancer
- Coloscopy
□ High risk: 2 yearly from 25
□ Moderate risk: yearly from 55
What are the benefits of genetic testing?
- Identifies highest risk
- Identifies non-carriers in families with a known mutation
- Allows early detection and prevention strategies
- May relieve anxiety
What are the risks and limitations of genetic testing?
- Does not detect all mutations
- Continued risk of sporadic cancer
- Efficacy of interventions variable
- May result in psychosocial or economic harm
