Familial cancer Flashcards
Causes of familial cancer
Genetics
Care taker genes- DNA repair, carcinogen metabolism.
Gatekeeper genes- cell cycle control
Environment
Macro- environment- chemical, viruses, radiation and physics agents.
Micro- environment- oxyradicals, hormones and growth factors.
What is the two hit hypothesis is cancer
both alleles must have a mutation for the cancer to develop.
why is it easier to develop cancer if you have I mutated gene (relate to 2 hit hypothesis)
In inherited cancer the first mutation is already present and therefore it is much easier to develop cancer
define peneterance
percentage of people with the gene change who develop the condition.
How does cancer develop on a cellular level
series of genetic changes within cells leading to abnormal behaviour and histology
function of gatekeeper genes
monitor and control cell division
function of caretaker genes
improve genomic stability (repair mutations
function of landscapers
control the surrounding stromal environment
what is the function of tumour suppressor genes
protect cells from becoming cancerous.
what is the function of oncogenes
regulate cell growth and differentiation.
examples of tumour suppressor genes
APC, BRAC1/2, TP53, Rb
do tumour suppressor genes gain or lose function to become cancerous
loss function
do oncogenes gain or lose function to become cancerous
gain function
examples of oncogenes
growth and signal transduction factors , RET gene
what is the name for the 2 hit hypothesis
Knudsons
Is cancer a autosomal dominant or recessive condition
autosomal dominant.
At a cellular level is cancer a dominant or recessive condition
recessive (2 hit hypothesis)
Give a example of a rare autosomal recessive condition
MYH associated polyposis, faconi anaemia and Ataxia telaniectasia.
What are 6 common types of mutation which can occur.
– Missense- incorrect amino acid due to single base change
– Nonsense- incorrect sequence causes shortening of protein due to single base change.
– Frame shift- frame shift of one DNA base results in abnormal amino acid sequence.
– Splice site mutations
– Large deletions and duplications
– Translocations
How do you take a history to help diagnose whether a cancer is familial or not.
- Include maternal and paternal sides
- At least 3 generations
- Children, siblings, parents, uncles, aunts, nephews, nieces, grandparents, cousins
- Types of cancer, age of diagnosis
- Confirm if possible – medical records, cancer registries, death certificate
does sporadic cancer develop at a young or old age
old.
does familial cancer develop at a young or old age
young.
examples of cancers which are mainly sporadic
cervical and lung
are other family members affected in a sporadic cancer
No
are other family members affected in a familial cancer
Yes.
what type are most adult cancers
epithelial
what type are most children’s cancers
haematogenous
what are the main disadvantages of genetic assessment
- Anxiety/unhappiness – self, children, other relatives
- Genetic discrimination
- Results may not lead to any change in management
- Financial costs to NHS
what is the difference between diagnostic and predictive testing
diagnostic testing (mutational analysis) usually performed on DNA from a relative affected with cancer to try to identify the familial mutation. If a mutation is identified in the family, predictive testing for the specific mutation may then be offered to other relatives to determine whether or not they are at risk
what is retinoblastoma
Childhood ocular cancer
what is the gene affected in retinoblastoma
Rb gene (TUMOUR SUPPRESSOR)
If both the eyes are affected in retinoblastoma, is the cancer likely to be familial or sporadic
familial.
what is FAP - familial adenomatous polyposis
Hundreds of bowel polyps (adenomas) from teens onwards
what cancer does FAP predispose to is untreated
bowel cancer.
what gene is affected in FAP
APC (TUMOUR SUPPRESSOR)
What type of inheritance is FAP
autosomal dominant.
what is used to diagnose FAP
colonoscopy
total colectomy
define polyposis
numerous polyps
What type of cancer does Hereditary Non-polyposis colorectal cancer cause
bowel cancer.
What type of inheritance is hereditary non-polyposis colorectal cancer
autosomal dominant.
what other cancers can you develop if you have hereditary non-poylposis cancer.
endometrial/ovarian/stomach/GU
what genes cause hereditary non polyposis colorectal cancer
Mismatch repair genes
MLH1 (50%), MSH2 (40%), MSH6 (10%), PMS1/2 (rare)
what criteria is used to diagnose hereditary non-polyposis colorectal cancer
Amsterdam criteria
What is the Amsterdam criteria.
- One member diagnosed with colorectal cancer before age 50 years
- Two affected generations
- Three affected relatives, one of them a first-degree relative of the other two
- FAP should be excluded-using histology.
- Tumours should be verified by pathologic examination
benefits of colonscopic screening in HNPCC
What is it used to detect
Removal of polyps/early detection of cancer improves survival
when should patient with HNPCC start to have colonoscopies.
Patients with HNPCC should have colonoscopy ~every 18-24 months from age ~25
HNPCC preventative surgery
Prophylactic colectomy is not usually recommended
However, women may consider hysterectomy +/- BSO
what are BRAC1 and BRAC2 involved in
DNA repair.
what inheritance is breast cancer
autosomal dominant.
Inheritance of BRAC1/BRAC2 (tumour suppressor genes) increases the risk of which cancers other than breast
. prostate, melanoma, male breast cancer
What can BRAC1/BRAC 2 carrier do.
- Breast screening – annual MRI 30-50, annual + mammography from ~35-40
- Risk-reducing mastectomies +/- reconstruction
- Risk-reducing BSO (ovarian screening probably no use)
- Lifestyle changes
- Pharmacological prevention studies
what genes does Li Fraumeni syndrome affect
P53 mutations
what inheritance is Li Fraumen
autosomal dominant.
what cancers does Li Fraumeni cause
Breast, sarcoma, brain, adrenocortical, leukaemia
why could Li Frumeni patient avoid radiotherapy
induces other cancers
what medication may potential prevent polyps
blood thinner
apirin)
signs of FAP
CHRPE (flat, pigmented spot within the outer layer of the retina), desmoid tumours, osteomas (benign tumour of new piece of bone growing)
what cancer does RB gene predispose to except retinoblastoma
osteosarcoma.
