Sesh 9- Neoplasia 3 Flashcards
(22 cards)
What % do extrinsic factors account for a population’s cancer risk?
85%
What are the 3 main categories of extrinsic carcinogens?
- Chemicals
- Radiation
- Infection
Which test is used to show initiators are mutagens and promoters cause prolonged proliferation?
The Ames test.
What is a pro-carcinogen?
A carcinogen requiring conversion to by liver cytochrome P450’s to become carcinogenic.
What is a complete carcinogen? Give an example.
A carcinogen that is an initiator and a promoter e.g. tobacco smoke.
By which two ways can radiation cause DNA damage?
- Directly e.g base change, double strand DNA breaks
2. Indirectly by free radical production
How can some infections be carcinogenic without directly affecting genes controlling cell growth?
- Can cause chronic tissue inflammation & the resulting regeneration is either:
- a promoter for pre-existing mutations
- or causes a new mutation via DNA replication errors
Why is HPV a direct carcinogen?
It expresses:
- E6 proteins- directly inhibits p53
- E7 proteins- directly inhibits retinoblastoma protein
How does HIV act as an indirect carcinogen?
-Indirectly lowers host immunity, making them vulnerable to other carcinogenic infections e.g. HHV8 causing Kaposi sarcoma
How can the 2 hit hypothesis be applied to familial cancers?
- 1st hit= germline mutation
- 2nd hit= somatic mutation
Does the 2 hit hypothesis apply to tumour suppressor genes or proton-oncogenes?
Tumour suppressor genes, as both alleles need to be inactivated (1 hit for each allele) to favour neoplastic growth.
What is the normal role of RAS?
- Is a G protein that activates a signalling cascade causing DNA to transcribe the cyclin D gene
- Gene then activates CDK which phosphorylates and inactivates retinoblastoma protein, allowing the cell to enter the cell cycle
What type of gene is the retinoblastoma (RB) gene?
Tumour suppressor
What is HER2?
A proto-oncogene encoding a growth factor receptor
What is xeroderma pigmentosum due to?
Autosomal recessively inherited mutations in DNA repair genes affecting nucleotide excision repair, leading to genomic instability.
What type of cancer are patients with xeroderma pigmentosum very susceptible to?
Skin cancer
What are the normal roles of BRCA1/2 genes?
Repair of double strand DNA breaks
What is the adenoma-carcinoma sequence?
- The step-wise accumulation of mutations in epithelium over time, leading to dysplasia, adenoma and then carcinoma formation.
- Cancer progression
- 1st hit inherited or somatic mutation of tumour suppressor gene
- 2nd hit= inactivation of normal alleles
- Then get homozygous loss of extra tumour suppressor genes
- Finally get additional mutations to form a carcinoma
What are the 6 hallmarks of cancer? Which one is exclusive to malignant neoplasms?
- Self-sufficiency in growth signals
- Resistance of anti-growth signals
- Induce angiogenesis
- Resist apoptosis
- Cell immortalisation (activation of telomerase genes)
- Invasion and metastases- exclusive to malignant
Which gene is mutated in patients with familial adenomatous polyposis (FAP)?
- APC on chromosome 5q21
- Encodes protein that binds to microtubule bundles
In which inherited disorder do patients develop colonic adenomas that carpet the mucosal surface, and often develop colon cancer before the age of 50 if untreated?
Familial adenomatous polyposis (FAP)
What type of gene is mutated in HNPCC?
DNA mismatch repair gene
