Genetics Flashcards
List some conditions that contribute to hereditary susceptibility to colorectal cancer?
Lynch Syndrome (HNPCC) Familial adenomatous polyposis (FAP)
What may mutations do to protein function?
Nonfunctional/missing protein
Reduced function
What is the definition of germline mutations?
- Inherited from single alteration in egg/sperm
- Heritable
- eg cancer family syndromes
What happens in oncogene mutation?
Accelerated cell division
Only 1 mutation needed for role in cancer development
What happens in tumour suppressor gene mutation?
1st mutation - Susceptible carrier
2nd mutation - Leads to cancer
What gene is lost in Familial adenomatous polyposis (FAP)?
APC
What is the main mechanism for familial cancer cancer development?
DNA Mismatch Repair
What is the lifetime risk of breast cancer in BRCA1 and 2 mutation carriers?
60-80%
Also risks of second primary, ovarian cancer, prostate cancer
What is the percentage chance of inheritance for an autosomal dominant condition in which one parent is affected?
50%
When should hereditary cancer syndromes be suspected in a patient?
- Cancer in 2 or more close relatives (on same side of family)
- Early age at diagnosis
- Multiple primary tumours
- Bilateral/multiple rare cancers
- Characteristic pattern of tumours (e.g. breast and ovary)
- Evidence of autosomal dominant transmission
In familial cancer syndromes, what is cancer family history used for?
- Accurate risk assessment
- Effective genetic counseling
- Appropriate medical follow-up
What interventions may be undertaken in a clinical genetics consultation?
- Increased awareness of symptoms / signs
- Lifestyle - diet, smoking, exercise,
- Prevention – oestrogen, aspirin use
- Screening
- Prophylactic surgery
What surveillance options are available for familial breast cancer?
- Breast awareness
- Early clinical surveillance 5yr < age 1st cancer in family
- Annual/clinical breast exams
- Mammography
- MR screening for high risk
What side effect can be observes from prophylactic oophorectomy in BRCA1/2 patients?
Surgically induced menopause
What is the recommended surveillance for a gene carrier at risk of colorectal cancer?
- 2 yearly colonoscopy from 25/35
- Prophylactic aspirin
What are some benefits to genetic testing?
- Identifies highest risk
- Identifies non-carriers in families with a known mutation
- Allows early detection and prevention strategies
- May relieve anxiety
What are some risks and limitations to genetic testing?
- Cant detect all mutations
- Continued risk of sporadic cancer
- Efficacy of interventions variable
- May result in psychosocial or economic harm
What gene is mutated in Li-Fraumeni Syndrome?
p53 gene
What are the modes of inheritance in multi-system disorders?
Chromosomal
- Numerical
- Structural
Single gene disorders
- Autosomal dominant
- Autosomal recessive
- X linked
Multifactorial
- Polygenic
- Environmental factors
Give some examples of autosomal dominant multi-system genetic disorders?
TS
NF1
Myotonic dystrophy
Why may many systems be involved in multi-system genetic disorders?
- Several genes with diverse functions are involved
- Single gene widely expressed in different tissues
- Single gene tissue-specific expression but tissue integral part of many different systems
What are some common problems in multi-system genetic disease?
- Variable expression within as well as between families
- Present to a large variety of different specialists
- Family history easily missed
Why may adults be referred for genetic consultation?
- Diagnosis
- Predictive testing
- Carrier testing/cascade screening
- Family history (including cancer)
- Fetal loss or recurrent miscarriages
List some mechanisms of adult onset genetic disease?
- Single gene
- Chromosomal
- Mitochondrial
- Multifactorial (+environment)
