9. Neoplasia 3 Flashcards by Amy Brown

What are the 5 leading behavioural and dietary risks associated with cancer?

high BMI
low fruit and veg intake 
low physical activity
smoking
alcohol

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What are the 3 categories of extrinsic factors that are cancer risks?

Infection
Chemicals
Radiation

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What intrinsic factors are linked to cancer?

Age
Sex
Hereditary

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What industrial carcinogen was used in dye manufacturing and what cancer did it cause?

2-napthylamine, bladder cancer

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What 3 things did 2-napthylamine show?

Time delay between carcinogen exposure and development
Risk depends on total carcinogen dosage
Carcinogens can be tissue specific

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What did the Ames test show?

Initiators are mutagens while promoters cause proliferation in target tissues

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What examples are there of mutagenic chemicals?

Alkylating agents
Aromatic amines
N-nitroso compounds
Natural products - asbestos
Polycyclic aromatic carbons

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What are pro carcinogens?

Chemicals that are converted to carcinogens in the liver by CYP 450 enzymes

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What are complete carcinogens?

Carcinogens that act both as a promotor and an initiator

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How can radiation cause cancer?

Indirectly through free radial generation

Directly through damage to bases and causing single stranded and double stranded DNA breaks

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What are the most common forms of radiation that people are exposed to?

Radon in earths crust
UV radiation from sunlight
Medical tests

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What 2 ways can infections cause cancer?

Directly by affecting genes that control cell growth
Indirectly by causing chronic damage and regeneration which acts either as a promotor or causes new mutations through replication errors.

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Which infection causes cancer directly?

HPV - cervical cancer

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How does HPV directly cause cancer ?

Produces E6 and E7 proteins.
E6 inhibits p53
E7 inhibits pRb

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How do Hep B and C cause cancer?

Indirectly by chronic liver injury and regeneration which increases accumulation of mutations.

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What cancer do Hep B and C cause?

Hepatocellular carcinoma

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How does Helicobacter pylori cause cancer?

Gastric inflammation causes increased risk of gastric adenocarcinoma

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How does HIV cause cancer?

Indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur

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What cancer is a HIV defining illness?

Kaposi’s sarcoma caused by Human herpes simplex

- purple lesions under the skin

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What cancer was used to demonstrate the 2-hit hypothesis?

Retinoblastoma

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Describe the 2 hit hypothesis of oncogenesis.

Mutations in TSG’s are inactivating, so mutations in both alleles are required for tumour growth.
In familial cancers, first hit is in germline mutation so only 1 somatic mutation is required to cause cancer, which is very likely.

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What are examples of oncogenes?

Ras
HER-2
c-myc

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How does Ras act as an oncogene?

It codes for a G-protein which causes transcription of Cyclin D, which activates CDK, causing phosphorylation of Rb and allowing constant entry to the cell cycle when it’s switched on.

What type of genes are Rb and p53?

Tumour suppressor genes

What is the role of Rb gene?

restrains cell proliferation by inhibiting passage through the restriction point.

How does c-myc act as an oncogene?

Transcription factor for a gene that promotes cell proliferation

How is Xeroderma pigmentosum (XP) inherited?

Autosomal recessive | Mutations in DNA repair genes that affect nucleotide excision repair (NER)

What cancer are patients with XP at risk of?

Skin cancer - very sensitive to UV

How is hereditary non-polyposis colon cancer (HNPCC) inherited?

Autosomal dominant | Germline mutations affect DNA mismatch repair genes

What cancer is HNPCC associated with?

Colon carcinoma

Which genes are associated with the inheritance of familial breast cancer?

BRCA1 and BRCA2

What process are the BRCA genes important for?

Repair of ds DNA breaks

What is the adeno-carcinoma sequence?

Colon carcinoma usually begins as a colonic adenoma which accumulates mutations to emerge as a carcinoma

What principle does the adenocarcinoma sequence demonstrate?

Most malignant tumours require alterations affecting a combination of multiple TS genes and proto-oncogenes over time (decades typically) = Cancer progression

What are the 6 hallmarks of cancer?

1. Self-sufficiency in growth signals 2. Resistance to anti-growth signals 3. No time limit on number of times it can divide 4. Induce angiogenesis 5. Resist apoptosis 6. Ability to invade and metastasise

What is classes as an enabling characteristic of cancer?

Genetic instability - acceleration of mutations

What growth factor stimulates angiogenesis?

VEGF

Which medical conditions are associated with increased risk of malignancy?

Ulcerative colitis Cirrhosis Hashimotos's thyroiditis Chronic atrophic gastritis

What cancer is Epstein-Barr virus associated with?

Burkitt's lymphoma - infects B cells | Not common in UK as no malaria

What cancers can be caused by asbestos?

Lung adenocarcinoma or mesothelioma

What is mesothelioma?

Cancer of the mesothelial cells (e.g in lung pleura)

How is asbestos thought to cause cancer?

A complete carcinogen - initiator and promotor | Pro-inflammatory

What was asbestos used for?

Roofing, insulation, fire proofing

Why is there an even higher increased risk of lung cancer in people who are exposed to asbestos AND smoke?

Carcinogens from smoke absorbed in asbestos fibres with carry them deeper into the lungs. Smoking paralyses cilia, prevents clearance.

How can you identify squamous cell carcinoma under a microscope?

Keratin production

What do basal cell carcinomas look like?

Pearly, nodular, raised, rolled-edge, volcano-like

How can you identify malignant melanoma under a microscope?

Melanin production visible

What are triple negative breast cancers?

HER2, ER and PR negative

What agent in cigarette smoke is carcinogenic, are they initiators or promoters?

Polycyclic aromatic hydrocarbons - initiators

What types of lung cancer are associated with smoking?

Small cell carcinoma | Squamous cell carcinoma

What effect does smoking have on the bronchial epithelium?

Causes metaplasia which can progress to squamous dysplasia and result in carcinoma in-situ and then invasive carcinoma.

What are the 2 inherited forms of colon cancer?

1. HNPCC | 2. Familial adenomatous polyposis (FAP)

What are the pathological features of FAP?

Patients develop thousands of colonic adenomas (polyps) that carpet mucosal surface which progress to colon cancer by 50 years old if not removed.

How is FAP treated?

Prophylactic colectomy

What gene is involved in FAP?

Adenomatous polyposis colon (APC) gene. | Autosomal dominant mutation of a tumour suppressor gene.

Which germline mutation is associated with osteosarcoma?

RB1