Genetic Predisposition to Cancer Flashcards
what actually is cancer
a genetic disease of somatic cells - happens by chance or due to environmental factors
what are a small proportion of cancers due to
an increased inherited predisposition to cancer
somatic mutations
(as opposed to germline mutations)
- occur in nongermline tissues
- are nonheritable
- cell not in germline develops some genetic alteration
germline mutations
(as opposed to somatic mutations)
- Present in egg or sperm
- Are heritable
- Causes cancer family syndromes
- in all cells of the body
what type of mutations are heritable
germline mutation
what are 3 genetic processes associated with cancer
- oncogenes
- tumour suppressor genes
- DNA damage-response genes
proto-oncogene
normal gene that codes for proteins to regulate cell growth and differentiation
what can mutations do to a proto-oncogene
change it into an oncogene
what can oncogenes do
accelerate cell division —> cancer
cancer arises when stuck in “on” mode
Tumour suppressor genes
function/role etc…
- Cell’s brake for cell growth
- genes inhibit cell cycle or promote apoptosis or both
- cancer arises when both brakes fail - Two-hit hypothesis
two-hit hypothesis
in order for a particular cell to become cancerous, both of the cell’s tumor suppressor genes must be mutated
if the two-hit hypothesis is true, what does that make tumour suppressor genes
recessive genes in effect
Two-hit hypothesis - explain each mutation
Normal genes (prevent cancer)
1st mutation (susceptible carrier)
2nd mutation or loss (leads to cancer)
what are DNA damage-response genes
the repair mechanics for DNA (DNA repair mechanics)
when does cancer arise in DNA damage-response genes
when both genes fail, speeding the accumulation of mutations in other critical genes
what does mismatch repair failure lead to
microsatellite instability (MSI)
Explain microsatellite instability (MSI)
- MMR (mismatch repair) - corrects erros that spontaneously occur during DNA replication (e.g. single base mismatches or short insertions/deletions)
- cells with anormally functioning MMR tend to accumulte errors
- MSI is the phenotypic evidence that MMR is not functioning normally - genetic hypermutability
benign
lacks ability to metastasize - rarely/never become cancerous
Dysplastic
benign but could procress to malignancy - pre-malignant
malignant
able to metastasize
what are 2 other, less common, causes of cancer
- autosomal recessive syndromes
- multiple modifier genes of lower genetic risk
features of retinoblastoma
- occurs in heritable and nonheritable forms
- Identifying at-risk ingants substantially reduces morbidity and mortality
- most common eye tumour in children
compare nonheritable vs heritable retinoblastoma (germline mutations in RB1 gene) - difference
Nonheritable - unilateral
Heritable - bilateral
Give some risk factors for breast cancer
- ageing
- family history - heritability
- early menarche, late menopause, nulliparity
- Estorgen use
- Diatery factors (e.g. alcohol)
- Lack of exercise
