Familiar Cancer Flashcards
What needs to occur for a cell to turn cancerous?
- Proliferation signalling,
- Avoidance of apoptosis,
- Bypassing replicative senescence
What is the function of tumour suppressor genes
They can have different functions
- Inhibition of cell through cell cycle,
- Promote apoptosis,
- DNA repair genes
What is the function of proto-oncogenes?
Regulate/activate cell growth and differentiation. If mutated, can become oncogenes (cancer causing)
What is the common genetic causes of cancer?
Most are autosomal dominant inheritance of an altered tumour suppressor gene
Explain the two hit hypothesis?
Both TSGs need to be inactivated to cause a phenotypic. 1 TSG mutation can be inherited, the second is acquired. Person with an inherited mutation is more likely to develop cancer at an earlier age as a second, sporadic mutation will result in no active TSGs left.
What should be an alarm for genetic cancer when taking a history?
- More than one person in the same family affected by similar cancers with an early age of onset.
- Multiple primary tumours,
- Early age of onset
What are two common mutations tested for with familial breast cancer?
BRCA1 and BRCA2. Less commonly TP53 and PALB2
What are the cancers and risks associated with BRCA1 mutations?
- Breast (50-80% risk of cancer by 70)
- Ovarian (20-50%)
(risks depend on family history and other genes)
What are the cancers and risks associated with BRCA2 mutations?
- Breast (50-80%)
- Ovarian (10-20)
- Male breast cancer (5-6%)
What is another genetic RF for development of breast cancer?
Many low-penetrance loci which offer an increased susceptibility for breast cancer.
There is about 72 different loci which are quite common but each only causes a small increased risk of BC.
What is the normal function of BRCA1 and 2 genes?
They are DNA repair genes which repair double strand breaks via homologous recombination.
When is DNA testing offered for identification of BRCA mutations?
If a person possesses at least a 10% risk. It is done via next generation sequencing
What are possible preventative measures for breast cancer?
- Examinations and screenings via mammography or MRIs.
- If person has BRCA mutation then they are offered prophylactic bilateral mastectomies and prophylactic oophorectomies
What are some additional genes which when mutated, can cause and increased risk of ovarian cancer
HNPCC genes (MLH1 or MLH2).
Name a new possible treatment for ovarian cancer
Olaparib
What is the most common cause of familial colon cancer?
Hereditary non-polyposis colon cancer. (most colon cancers are AD)
Describe features of hereditary non-polyposis colon cancer (Lynch syndrome)
Occurs due to AD mutation in the DNA mismatch repair genes (important for accurate DNA replication)
- Usually only a few polyps (less than 10), which may or may not also be present on uterus, stomach and ovaries.
What are the risks if a person has a MMR gene mutation?
Males - 80-90% lifetime risk of colon cancer.
Females - 40% of cc, 50% risk of endometrial cancer and 4% risk of ovarian
What screening is offered for those with MMR gene mutations and are therefore at risk of HNPCC?
Colonoscopies.
- 2 yearly colonoscopies from age 25.
- 2 yearly endoscopies from age 50.
(NB: Aspirin mat reduce risk of colorectal cancer)
What are the common mutations which cause HNPCC?
They are different DNA mismatch repair (MMR) genes
-MLH1 (50%)
- MLH2 (40%)
- MSH6 (7-10%)
What is another autosomal dominant cause of genetic colon cancer and its features?
Familial Adenomatous Polyposis. It is caused by a mutation in the APC gene.
- 80% have congenital hypertrophy of the retinal pigment epithelium.
- Offered annual bowel screening from age 11
What is an autosomal recessive cause of colon cancer
- MUTYH polyposis, an autosomal recessive (remember this!) disease which can result in the development of 15-200 polyps. (Mild FAP)
- High risk of carcinomas so offered 2 yearly colonoscopy
