Clinical Genetics Flashcards
what percentage of breast cancers are familial or heritable?
5-25%
what percentage of ovarian cancers are familial or heritable?
5-10%
define a germline mutation, and its consequence in offpsring
mutation in sperm/egg gene - will be present in all cells of offspring, can cause familial cancers
define a somatic mutation, and its consequence in offspring
mutation in a developed cell - will only be present in one cell, not heritable
which main types of genes involved in the cell cycle are involved in cancer development? where do they act in the cell cycle and how?
oncogenes - promote cell growth during G1 phase
tumor suppressor genes - halt DNA synthesis until cell is ready - act before S phase
DNA repair genes - act after S phase and before G2 phase, check DNA synthesis is correct
many familial cancers are caused by problems in which types of genes involved in the cell cycle?
DNA repair genes
explain the two-hit theory in cancer development
- an insult causing loss/damage to one allele will cause predisposition to cancer
- a second insult to the other copy of that allele will cause cancer development
familial adenomatous polyposis is caused by loss of which gene? (name and type of gene)
APC - a tumor suppressor gene
retinoblastoma is caused by damage to which gene (name and type of gene)
retinoblastoma gene - a tumor suppressor gene
what is Lynch syndrome also known as?
it is hereditary non-polyposis colorectal cancer
mutation of which genes leads to Lynch syndrome?
mutation in DNA mismatch repair genes
what cancers are prevalent in Lynch syndrome?
colorectal ovarian endometrial stomach biliary tract
which genders are linked to which genetic mutation for breast cancer? what other cancers may occur?
women - BRCA1; breast and ovarian
males - BRCA2: breast and prostate
what is the unusual medication which seems to be effective in reducing colorectal cancer risk in patients with Lynch syndrome?
daily aspirin for 2+ years
name the characteristic features of autosomal dominant disorders
- no skipped generations
- 50% chance for offspring to carry disorder
- equal transmission by men and women
when is a patient at high risk of having a hereditary cancer syndrome?
- multiple primary tumours
- pattern of rare/specific tumours
- 2+ cancers in close members on same side of family
- young age at onset
- evidence of autosomal dominant transmission
how is hereditary cancer incidence kept to a minimum?
- early and regular screening
- prophylactic surgery
- genetic testing
name two types of genetic testing that can be done to test for Lynch syndrome
- immunohistochemistry (IHC)
- mini satellite instability (MSI)
what causes Li-Fraumeni syndrome?
mutation in P53, a tumor suppressor gene
what cancers are associated with Li-Fraumeni syndrome?
SBLA - sarcoma, breast, leukaemia, adrenal gland
what modes of inheritance are possible in multi-system genetic diseases?
- chromosomal
- single gene
- multifactorial
in clinical genetics, why do some genetic conditions affect more than one system?
- because various genes are involved (chromosomal abnormalities)
- because the faulty gene is present in many types of tissues
- because the faulty gene is specific to one tissue, but that tissue is found in many systems
in clinical genetics, what are some problems associated with diagnosing genetic multi-system diseases?
- they can present differently within the same families
- they can present to many different specialties
- they can be difficult to identify from a family history
what mode of inheritance do tuberous sclerosis, neurofibromatosis type 1 and myotonic dystrophy present?
autosomal dominant inheritance
