Genetic Predisposition to Cancer Flashcards
Cancer is a ______ disease of somatic cells.
Genetic
Is cancer common?
Yes
What are the 2 main reasons for cancer?
Chance
Environmental factors
Where do somatic mutations occur?
Nongermline tissues
Where are germline mutations present?
In egg or sperm
What type of mutation is heritable?
Germline
What do tumours begin as?
Mutation in one cell
What are the 3 processes associated with cancer?
Oncogenes
Tumour supressor genes
DNA damage respose genes
What do proto-oncogenes normally code for?
Proteins to regulate cell growth and differentiation
What do mutations change proto-oncogenes into?
Oncogene
What can oncogenes do?
Accelerate cell division
What do tumour suppressor genes do?
Inhibit cell cell or promote apoptosis
What do DNA damage response genes do?
Repair mechanics for DNA
Why does cancer arise when both DNA damage response genes fail?
Speeds the accumulation of mutations in other critical genes.
What does mismatch repair failure lead to?
Microsatellite instability.
MSI is the phenotypic evidence that MMR is not ______ normally.
Functioning
Define dysplastic.
“Benign” but could progress to malignancy.
What is a dominantly inherited cancer syndrome by oncogenes?
Thyroid cancer
What is a dominantly inherited cancer syndrome by tumour suppressor genes?
Breast/ovarian cancer
What is a dominantly inherited cancer syndrome by DNA repair?
Lynch Syndrome
What type of disease needs the copy from both parents?
Autosomal recessive
De novo mutation occurs in ______ cell of parent
Germ
In hereditary cancer, what is wrong with penetrance?
Often incomplete
What is retinoblastoma?
Most common eye tumour in children.
What does identifying children with retinoblastoma early do?
Reduce morbidity and mortality.
What are the top 3 risk factors of breast cancer?
Ageing
Dietary Factors
Family History
Do genes work in isolation?
No
What is the average number of mutations in breast cancer?
20,000
How many mutations do we have most days?
60,000
What is the risk of breast cancer of people with BRCA1?
50-85%
What is the risk of secondary primary breast cancer of people with BRCA1?
40-60%
What is the risk of ovarian cancer of people with BRCA1?
15-45%
What is the risk of breast cancer of women with BRCA2?
50-85%
What is the risk of ovarian cancer of women with BRCA2?
10-20%
What is the risk of breast cancer in men with BRCA2?
6%
What are the three highest risk factors of colorectal cancer?
Ageing
Personal history of CRC
High fat, low fibre diet
What is the carcinoma sequence?
Normal epithelium
Hyperproliferative epithelium
Adenoma
Carcinoma
Define non-polyposis.
Few to no adenomas
Define polyposis.
Multiple adenomas
Where do sporadic HNPCC cancers usually occur?
Exit part of colon
What type of cells usually have extracolonic cancers?
Those which have a high turnover i.e ovary
Sebaceous skin tumours are always ______.
Benign
What is the estimated penetrance for adenomas in FAP?
Greater than 90%
Untreated polyposis of FAP leads to ___% risk of cancer.
100
What would 4 or more CHRPE mean?
A mutation in the ACP gene.
Is attenuated FAP associated with CHRPE?
No
What are the physical features of attenuated FAP?
Upper GI lesions
What is recessive MYH polyposis similar to?
GI features of attenuated FAP
What can multiple modifier genes of lower genetic risk explain?
Families with history of cancer and no identified mutation.
Difference in cancer penetrance in families.
What 3 ways are there to manage cancer risk?
Surveillance
Surgery
Chemoprevention
What are 3 problems with gene tests?
Not always possible
Mutation may not be related
Variants are unknown significance
What are the two types of sequences?
Exome
Genome
