Genetic predisposition to cancer Flashcards
What are oncogenes?
Genes that regulate cell growth
How many oncogene mutations are required for cancer development?
1 is sufficient
What are tumour suppressor genes?
Genes that prevent cancer - slows down cell cycle and causes apoptosis in presence of irreparable DNA damage
How many tumour suppressor gene mutations are required for cancer?
2
What are the steps in cancer development?
Normal epithelium Hyper-proliferative epithelium Early adenoma/benign Intermediate adenoma/benign Late adenoma/benign Carcinoma Metastasis
What is the main mechanism for familial cancer?
DNA mismatch repair
What is Lynch syndrome?
Hereditary Non-Polyposis Colon Cancer
Mutation in mismatch repair
Increased risk of colorectal, endometrial, urinary tract, ovarian, and gastric cancers
What are associated cancers with BRCA1 and 2?
Breast cancer
Second primary breast cancer
Ovarian cancer
BRCA2 = prostate and breast cancer in males
What is autosomal dominant inheritance?
More prominent than recessive allele, equally transmitted by men and women
When should hereditary cancer syndrome be suspected?
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
Evidence of autosomal dominant transmission
What should be done in clinical genetics consultation?
Go through family history Risk estimation Explanation of basis of risk Interventions - increased awareness, lifestyle - diet, smoking, exercise, prevention, screening Genetic testing if high risk
What are surveillance options for breast cancer?
Breast awareness
Early clinical surveillance 5 years before first cancer in family
Mammograohy
What are benefits of prophylactic mastectomy in BRCA1/2 carriers?
Remove most but not all breast tissue
Significantly reduce breast cancer risk in women with family history
Reduces BRCA1 carrier incidence of breast cancer to 5%
What are benefits to genetic testing?
Identifies high risk
Identifies non-carriers in families with a known mutation
Allows early detection and prevention strategies
May relieve anxiety
What are 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
