Genetic Predisposition to Cancer Flashcards
What is extragenic DNA?
repetitive sequences
control regions
function mostly unknown
spacer DNA between genes
What percentage of breast cancer is attributed to hereditary?
5-10% = hereditary 15-20% = family clusters
the remaining of breast cancers are sporadic
What percentage of ovarian cancer is attributed to hereditary?
5-10% = hereditary
the remaining is sporadic
What are the stages of the cell cycle?
G0= resting G1= cell growth S = synthesis G2= checkpoint/ repair M= mitosis
What are the features of gremlin mutations?
present in egg/sperm
All cells affected in offspring
Are heritable
Cause cancer family syndromes
What are the features of somatic mutations?
Occur in non-germline tissues
are non-inheritable
What are oncogenes?
what is the significance of mutations?
Gene that has the potential to cause cancer
1st mutation = leads to accelerated cell division
1 mutation is sufficient for role in cancer development
What happens if there is a mutation in tumour suppressor gene?
Normal tumour suppressor genes= prevent cancer
1st mutation= susceptible carrier
2nd mutation or loss= leads to cancer
DNA repair is insufficient and cancerous cells can arise e.g. colon cancer
Describe the features of Lynch syndrome (HNPCC)
mutation in mismatch repair genes
excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers
good opportunity for prevention by colonoscopy
often early age of onset (diagnosed ~45)
What is the associated risk of cancers with BRCA1 and 2 genes?
Breast cancer risk 60-80%
Ovarian cancer 20-50%
Males- increase risk of prostate cancer and breast cancer
When are you to suspect hereditary cancer syndrome?
- cancer in 2 or more close relatives
- early age at diagnosis
- multiple primary tumours
- bilateral or multiple rare cancers
- characteristic pattern of tumours
- evidence of autosomal dominant transmission
What is the importance of taking a cancer family history?
Gives an accurate risk assessment
Effective genetic counselling
Appropriate medial followup
What are the outlines of breast cancer surveillance?
Early clinical surveillance: 5 years before age of the earliest cancer in the family
Mammography:
mod/high risk= 2 yearly from 35-40
then yearly from 40-50
High risk only 18 monthly from 50-64
What is prophylactic mastectomy?
Removal of most but not all breast tissue
Significantly reduces breast cancer risk in women with a FH
(BRCA1 mutation-positive women breast cancer incidence reduced to 5%)
What is prophylactic oophorectomy?
What is the consequence of it?
eliminates risk of primary ovarian cancer but peritoneal carcinoma may still occur
Induces menopause therefore HRT until age 50 is needed
