PoD - Genetic Predisposition to Cancer Flashcards
1
Q
what is cancer genetics?
A
- cancer is a genetic disease of somatic cells
- most cancers happen by chance or due to environmental factors
- small proportion of cancers happen because of an increased inherited predisposition
2
Q
what type of mutations are associated with cancer?
A
- somatic mutation (occur in non-germline tissue and are non-inheritable)
- gremlin mutations (present in egg/sperm, can be inherited and can cause cancer family syndromes)
3
Q
what are tumours?
A
- tumours are clonal expansions
- develop over time
- every tumour is unique, tend to be grouped together in relation to the genes that are mutated
4
Q
what are oncogenes?
A
- proto-oncogenes - normal gene that codes for proteins to regulate cell growth and differentiation
- mutations can change a proto-oncogene into an oncogene
- oncogenes accelerate cell division
- 1 mutation is sufficient for cancer development
- cancer arises when stuck in “on” mode
5
Q
what are tumour suppressor genes?
A
- they are the cell’s brakes for growth
- genes inhibit cell cycle or promote apoptosis or both
- cancer arises when 2 mutations occur
- 1st mutation means individual is susceptible to develop cancer, 2nd mutation leads to cancer
6
Q
what are DNA damage-response genes?
A
- try to repair mutated DNA
- cancer arises when both genes fail, speeds the accumulation of mutations in other critical genes
7
Q
what does benign mean?
A
- tissues that rarely or never become cancerous
- lacks ability to metastasise
- can still cause health problems due to pressure on other organs
8
Q
what does dysplastic mean?
A
- benign but could progress to malignancy
- cells show abnormality go appearance and cell maturation
- pre-malignant
9
Q
what does malignant mean?
A
- cancerous
- able to metastasise
10
Q
describe what happens in retinoblastoma?
A
- most common eye tumour in children
- occurs in heritable and non-heritable forms
- identifying at-risk infants reduces morbidity and mortality - early detection means tumours can be treated with laser rather than eye removal
- occurs in germline mutations in the RB1 gene
- non-heritable = unilateral, no family history, diagnosis at 2 years
- heritable = usually bilateral, family history in 20% of cases, diagnosis less than 1 year, likelihood of developing second cancers
11
Q
what increases risk of breast cancer?
A
- ageing, family history, menopause, oestrogen use, lack of exercise
- genes contributing to familial breast cancer - BRCA1/2
- BRCA1 - 50-85% likelihood of developing breast cancer (early age). increases risk of ovarian cancer
- BRCA2 - 50-85% risk of breast cancer, 6% of male breast cancer, 10-20% ovarian cancer, increased risk of prostate/pancreatic cancers
12
Q
what increases risk of colorectal cancer?
A
- ageing, history of CRC or adenomas, high-fat/low-fibre diet, inflammatory bowel disease
- genetic changes
13
Q
list types of CRCs
A
- hereditary non-polyposis colorectal cancer (HNPCC) results from failure of mismatch repair genes
- hereditary polyposis CRC can have varying degrees of adenomas (FAP=severe polyps/AFAP=less severe/MAP=varying degrees of polyps)
14
Q
what are the clinical features of HNPCC?
A
- early but variable age at diagnosis
- tumour site throughout colon (not descending colon)
- high likelihood of extracolonic cancers (endometrium, ovary, stomach, UT, bowel)
15
Q
what are the clinical features of FAP
A
- Estimated penetrance for adenomas >90%
- Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
- CHRPE (congenital hypertrophy of the retinal pigment epithelium) may be present
- Untreated polyposis leads to 100% risk of cancer
