Genetics - Cancer Flashcards
What proportion of breast cancer is hereditary?
5-10% hereditary
15-20% Family clusters
What proportion of ovarian cancer is hereditary?
5-10%
What are the causes of colorectal cancer?
Sporadic 65%
Familial 10-30%
Lynch syndrome/HNPCC 5%
FAP 1%
What mutations cause cancer?
Germline (heritable)
Somatic (sporadic)
What are germline mutations?
Inherited from single alteration in zygote
What oncogene is associated with Leukaemia?
ABL
BCR-ABL Fusion Protein
How many oncogene mutations are required for cancer growth?
1
How many Tumour suppressor gene mutations are required for cancer growth?
1 - carrier
2nd or loss - cancer
What is the main mechanism of familial cancer?
Faulty DNA mismatch Repair
What is the cause of Lynch syndrome/HNPCC?
Mutation is mismatch repair genes
How does HNPCC present?
Colorectal polyps/adenomas
What is the normal function of oncogenes?
Regulate cell growth
HNPCC/Lynch increases the risk of what?
Cancer - Colorectal
Endometrial
Urinary tract
Ovarian
BCRA 1 and 2 increase lifetime risk of what cancers?
Breast (60-80%)
Second primary Breast (40-60%)
Ovarian cancer (20-50)
BRCA 2 increases the risk of what cancers in males?
Prostate cancer
Breast cancer
When should hereditary cancer syndromes be suspected?
Cancer in 2 or more close relatives
Early age diagnosis
Multiple primary tumours
Characteristic patterns
Most inherited cancers are inherited in what pattern?
Autosomal dominant
What is the cancer genetics process?
Obtain detailed FH - pedigree
Confirmed cancer diagnosis
Risk estimation
Counselling
What interventions can be applied to reduce the risk in a high risk patient?
Increased awareness of signs/symptoms Lifestyle changes Prevention Screening Prophylactic surgery
What are the breast cancer surveillance options?
Begin 5yr under age of 1st cancer in family
Annual breast exams
Mammogram (18 monthly for high risk)
What is the incidence of breast cancer in BRCA 1+ve women post-prophylactic mastectomy?
5%
What are the colonoscopy recommendations in CRC families?
Gene carrier 2yearly from 25
Prophylactic aspirin
What genetic tests are used for Lynch syndrome?
Immuno-histochemistry for microsatellite instability
Need 2 somatic hits
What are the benefits of genetic testing for cancer?
Identify high risk
Identifies non-carriers
Allows early detection
May relieve anxiety
What are the limitations of genetic testing for cancer?
Does not detect all mutations
Continued risk of sporadic caner
Psychosocial/economic harm
When do you refer a patient to genetic counselling if their parent had cancer?
If the parent was diagnosed <40y/o
