Genetics - predisposition to cancer Flashcards
Clinical approach to management of cancer and predisposing syndromes, including FAP, breast, ovarian and colon cancer.
Risk estimation for those at moderate risk, role of genetic testing.
Low penetrance genes and future possibilities.
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List the causes of CRC from most common to least common (5)
Sporadic Familial Lynch syndrome (aka HNPCC) Familial adenomatous polyposis (FAP) Rare CRC syndromes
Cancer arises what either … or … mutations
germline or somatic (non-inheritable)
Oncogenes affect which phase of the cell cycle
G1 (cell growth phase) of interphase (before mitotic phase)
Tumour supressor genes affect which phase of the cell cycle
Prevent G1 (cell growth) from progressing into S (DNA replication) phase
DNA repair genes affect which phase of the cell cycle
S (DNA replication) phase
List the phases of the cell cycle
Interphase - G1, G0, S, G2
Mitotic phase - prophase, metaphase, anaphase, telophase, cytokinesis
With oncogenes, how many mutations on a chromosome is enough for cancer development
Same question for tumour suppressor genes
1 for oncogenes
2 for tumour supressor genes, 1 makes you a susceptible carrier
What is the main mechanism for familial cancers
Faulty DNA mismatch repair genes so mutation introduced by unrepaired DNA
What is the mechanism for lynch syndrome (aka HNPCC)
Mutation in mismatch repair genes
Is Lynch syndrome autosomal dominant or recessive
Autosomal dominant
Lynch syndrome most commonly gives rise to CRC, what other cancers can it give rise to?
Endometrial (next commonest), gastric, biliary tract, ovarian, breast, small bowel (intestinal), urinary tract and more
What cancers do the BRCA genes increase risk of in males
Prostate
Breast
What is mendelian inheritance + what are the 4 modes of mendelian inheritance
The manner by which genes and traits are passed from parents to their children
Autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive
When to suspect hereditary cancer syndromes like Lynch syndrome
Cancer in 2 or more close relatives on same side of family
Young age diagnosis
Multiple primary tumours
Bilateral or rare cancers
Characteristic pattern of tumours, e.g. breast + ovary
Evidence of autosomal dominant transmission
What’s more common - hereditary or sporadic cancers
Sporadic
Hereditary cancers are quite a small proportion
4 steps in the process of cancer genetics
Obtain detailed family history
Confirm diagnoses of cancer
Risk estimation
Counselling
Consider genetic testing in what group of people
High risk, not low or moderate (estimate risk for these)
BRCA1/2 gene carriers can get what prophylactic procedures
Mastectomy - significantly reduces breast cancer risk in those with a FH of it
Ooophorectomy - eliminates risk of primary ovarian cancer, but induces menopause early
A gene carrier of CRC is recommended to get a colonoscopy how frequently
2 yearly from 25
Someone with a moderate risk of CRC is recommended to get a colonoscopy how frequently
5 yearly from 50
Ways to genetically test for Lynch syndrome (2)
Immunohistochemistry (IHC) for mismatch repair genes
Microsatellite instability testing (MSI)
What prophylactic drug can be given to prevent CRC
Aspirin
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
