Cancer Genetics Flashcards
1
Q
are cancers hereditary?
A
- no, they are typically acquired, 5% are hereditary
- however, predispositions can be hereditary
2
Q
cancer predisposition
A
- all cancers are DNA mutations, typically found in somatic cells, therefor they are not passed on
- predisposition from autosomal dominant cancer mutations which can be familial, these show incomplete penetrance and variable expressivity
- most cancers require two mutations
3
Q
Knudson’s two hit hypothesis
A
- this research was done by studying early onset, bilateral retinoblastomas vs late onset, unilateral retinoblastomas
- knudson hypothesized that it takes two mutations in the same gene to make that gene cancerous
- however, if you inherit one form of this mutated gene to begin with, then your chances of acquiring a “second hit” are much higher
4
Q
Loss of function mutation
- definition
- hetero/homozygosity
- 2 classes
A
- more common for inherited predisposition syndromes
- loss of both copies of the gene is necessary to cause cancer
- one example or type are tumor suppressor genes (p53, Rb, NF1, APC), they restrain cell growth
- another is mismatch repair genes
5
Q
Gain of function
- definition
- what genes fall in this category
A
- rarely inherited (are exceptions)
- a single somatic gene mutation is all that is needed to cause tumorigenesis
- typically growth and transcription factors
- oncogenes (proto-oncogenes)
6
Q
Process of seeing a patient in a cancer genetics clinic
- history
- patterns
- discussion
- insurance
- maintain…
- family
A
- analyze as extensive of a family history as possible
- note patterns of early onset cancer or combinations of specific cancers which correlate to genetic predisposition
- discuss risks, benefits, limitations of DNA testing
- work with insurance companies to get pre approval for testing
- mainting confidentiality
- counsel extended family members
7
Q
red flags for hereditary cancers
A
-early onset
8
Q
cancer combinations associated with BRCA1,2
A
breast, pancreatic, and ovarian
9
Q
combinations associated with p53
A
breast, sarcomas, leukemia and brain
10
Q
red flags for BRCA
A
- early onset breast cancer
- bilateral breast cancer
- male breast cancer
- ovarian cancer at any age
- breast or ovarian cancer in women of ashkenazi jewish descent
- families with combinations of breast, ovarian, and pancreatic cancer
- families know to have the mutation
11
Q
testing people of young age
A
-this seems to be advised against as the brain is not yet fully developed and news of increased risk of cancer could change their life completely and be detrimental to their mental health
12
Q
benefits of BRCA testing
- breast care, what can you take, operation
- ovarian care, what can you take, operation
- screening
A
Breast care
- frequent self and clinical examinations
- earlier onset and increased frequency of imaging
- tamoxifen for prevention of breast cancer
- prophylactic mastectomy can be performed
Ovarian Care
- oral contraceptive use
- CA-125 and tranvaginal ultrasound
- bilateral oophorectomy after completion of childbearing (also decreases breast cancer risk)
Screeening for other cancers like prostate, male breast, and melanoma)
13
Q
Concerns regarding BRCA testing
- for the symptomatic individual
- asymptomatic individual
A
symptomatic
- guilt and concern over passing gene on
- worry of risk of developing additional cancer
- medical insurance discrimination is NOT an issue (they know you have had cancer). federal genetic information nondiscrimination act
asymptomatic
- physiological distress
- medical insurance discrimination is not an issue
- life insurance discrimination however, is an issue. companies raise rates based on actuarial assessment of risk
14
Q
limitations of DNa testing
- variants
- negative and positive results
A
- can find variants of unknown significance
- a negative BRCA test does not rule out the possibility of an inherited predisposition to cancer
- even if positive, it can not predict when or if you will get cancer
15
Q
colorectal cancer
- fancy name
- young age phenotype
- chances of developing cancer in association with phenotype
- inheritance, characterization
A
- colorectal cancer
- familial adenomatous polyposis (FAP or APC)
- multiple polyps in colon from young age
- over time polyps develop into cancer
- number of carcinomas is low but the potential is high if there is a lot of polyps
- chromosome 5
- inherited as AD, shows variable penetrance
