Clinical Cancer Genetics Flashcards
1
Q
The basics of DNA and the genetic code
A
- Made of 4 nucleotides which are A, T, C and G
- Humans have a lot of genetic variation which are common (SNPs)
- This is what makes humans unique from one another
- Genetic variation may influence our chances of developing disease
2
Q
Cancer statistics
A
- Cancer is a common disease in humans
- There is a 1 in 2 lifetime risk of developing cancer
- Most cancers however are sporadic meaning they are due to acquired (somatic) mutations within a cell. - These mutations allow the cell to divide and give a growth advantage so they keep proliferating abnormally.
- Some genetic mutations change we are born with however, may influence out lifetime cancer risk. These are inherited risk.
3
Q
What are sporadic cancers?
A
65% of cancers are sporadic.
- Acquired mutations in cancer genes drive the cell to become cancerous.
- These changes are not inherited because they are acquired sometime throughout our lifetime, during cell division.
4
Q
How do internal and external factors cause sporadic cancers?
A
- Internal and external factors can play into this and help drive a cell to become cancerous such as reactive oxygen species and ineffective DNA repair mechanisms (for internal) and UV light and cigarette smoke (for external).
5
Q
What are inherited cancers?
A
They are cancers that are caused by genetic changes that we are born with which increases the risk of developing cancer. The higher risk changes are cancer predisposition genes.
6
Q
What is the genetic architecture of disease graph?
A
- This graph shows how common a cancer gene is in the population and the chances of getting cancer.
- High risk cancer predisposition genes are normally very rare however, if a person had them, they would have a high chance of developing cancer. e.g. a germline mutation in the p53 gene gives 9/10 chance of developing cancer.
- Low risk common genetic variations are common within the population but play a very small in the chances of getting cancer. However, the accumulation of these such as having 30 common variation, increases the chance of the individual of getting cancer. But having an individual with that many common variants is still rare.
7
Q
What is multifactorial risk?
A
- When there is increased clustering of the same type of cancer in a family there might be increased multifactorial risk.
- This is when there are SNPs that are more common in cases than in controls and therefore the risk of developing cancer is increased from the normal distribution.
8
Q
What are high risk predisposition genes?
A
- BRCA: Breast cancer, Ovarian
- Lynch: Colon
- CDKN2A: Melanoma
- RET: Medullary thyroid
- RB1: Retinoblastoma
- BRCA2: Prostate and Pancreatic
9
Q
How are inherited cancer risk assessed?
A
- Family history assessment
- Testing of the cancer
10
Q
Why is taking a family history assessment important?
A
- It is important because we share half our genetic information with our first-degree relatives.
We look at three generations to get the most amount of information and whether they have multiple cancers or one. - Some cancers have young age of onset. Such as breast cancer, women are unlikely to develop sporadic cancers at a young age. However, look at high risk genes for example BRCA mutation, there increases the risk of both breast and ovarian cancer and therefore you can start looking for patterns.
- Ethnicity is also a factor - certain ethnic backgrounds are more likely to get cancer than others.
11
Q
Why is it important to test cancers?
A
- Certain pathology subtypes of cancers increase risk of high-risk cancer pathology genes.
- High grade serous ovarian cancer: BRCA1/2
- Medullary thyroid cancer: RET
- Triple negative breast cancer: BRAC1/2
- Type 2 papillary kidney cancer: FH
- High grade serous ovarian cancer: BRCA1/2
- Molecular testing of the tumour itself may identify genetic changes which could indicate inherited risk.
- For example, immunohistochemistry of mismatch genes in lynch syndrome. BRCA genes sequencing in ovarian cancer.
12
Q
What needs to be considered when making a decisions to assess on?
A
- Is there an increased inherited risk of cancer?
- How high is the risk?
- Does the patient need genetic testing to look for high risk cancer predisposition genes?
- Does the patient and/or their relative need extra screening or other measures to reduce cancer risk?
13
Q
What type of screning would be offered to a person with a multifactorial/polygenic risk?
A
- When a gene test comes out negative but there is a lot of cancer in the family or when there is more cancer in the family than we would expect by chance but the risk is not high enough to meet the high gene risk criteria. The famiy would be offered screening prevention and early detection advice (SPED).
14
Q
What can be offered to people who are at high risk for cancers?
A
Chemoprevention
- taking medication to reduce breast cancer risk: Tamoxifen and SERM for breast cancer. This has side effect of their own.
- Aspirin for colorectal cancer
15
Q
What are the implications that should be considered when genetic testing?
A
Implications for individuals:
- Recurrence risks
- Risks of other cancer
Implications for relatives:
- How to share the information
- Concerns about children because they will have a high chance of inheriting the same gene
- Family planning options
