Week 10 - neoplasia 3 Flashcards
What are the main behavioural and dietary cancer risks?
- High BMI
- Low fruit and vegetable intake
- Lack of physical activity
- Tobacco use
- Alcohol use
What are the main types of extrinsic carcinogens?
- Chemicals
- Radiation
- Infection
Describe chemical carcinogens
- E.g. Polycyclic hydrocarbons, aromatic amines
- Some chemicals are pro-carcinogens and are only converted to carcinogens by the cytochrome P450 enzymes in the liver
- There is a long delay between carcinogen exposure and malignant neoplasm onset
- The risk of cancer depends on total carcinogen dosage
- There is sometimes organ specificity for particular carcinogens
Describe radiation carcinogens
- Any type of energy travelling through space
- Some forms are mutagenic
- UV light doesn’t penetrate deeper than the skin so is particularly important for skin cancer
- Ionising radiation strips electrons from atoms (e.g. X Rays and nuclear radiation)
- – It can damage dna directly and indirectly by generating free radicals
- – Can damage dna bases and cause single/double strand dna breaks
Describe infection carcinogens
- Some directly affect genes that control cell growth
- Some indirectly cause chronic tissue injury
- – The resulting regeneration acts either as a promoter for any pre-existing mutations or causes new mutations from DNA replication errors
Give some examples of infection carcinogens
- Human papilloma virus
- – Strongly linked to cervical cancer
- – Direct carcinogen
- – Expresses E6 and E7 proteins that inhibit p53 and pRb protein function respectively (important for cell proliferation)
- Hep B and C
- – Indirect carcinogens
- – Cause chronic liver cell injury and regeneration
- Bacteria and parasites
- – Can directly lead to neoplasms
- Helicobacter pylori
- – Causes chronic gastric inflammation
- Parasitic flukes
- – Inflammation in bile ducts and bladder mucosa
- – Increases the risk for gastric, cholangio- and bladder carcinomas
- Human immunodeficiency virus
- – Acts indirectly by lowering immunity and allowing other potentially carcinogenic infections to occur
What are tumour suppressor genes?
Genes that inhibit neoplastic growth
- Act like brakes on tumour growth
- Both alleles must be inactivated (need 2 hits)
What are oncogenes?
Genes that enhance neoplastic growth
- Abnormally activated versions of normal genes called proto-oncogenes
What are the stages in carcinogenesis?
- Initiation
- – Some chemical carcinogens can be initiators (they are given first)
- – They are mutagens
- Promotion
- – Promoters are given following initiators
- – Cause prolonged proliferation
- Cancer progression
- – The accumulation of multiple mutations in malignant neoplasms
What are the 6 hallmarks of cancer?
- Self sufficiency in growth signal
- Resistance to growth stop signals
- No limit on the number of times a cell can divide
- Sustained ability to induce new blood vessels
- Resistance to apoptosis
- The ability to invade and produce metastases
What is the enabling characteristic in malignant neoplasms?
Genetic instability
What is carcinogenesis?
Causes of cancer
- Combination of intrinsic host factors and extrinsic factors
- Much of the increased cancer incidence is due to prolonged life span
How is retinoblastoma caused?
Can be inherited
- Has a dominant pattern of inheritance
- Runs in families and can occur sporadically
- 1st hit was delivered through the germline, 2nd hit is a somatic mutation
Can occur sporadically
- Requires both hits to be somatic mutations and to occur in the same cell
How does familial breast cancer occur?
Associated with either BRCA1 or BRCA2 genes
- Important for repairing double strand breaks
What is xeroderma pigementosa and how can it be caused?
- Increased sensitivity to UV damage
- Develop skin cancer at a young age
- Germline mutations in DNA repair genes
What is RAS?
An oncogene
- It encodes a small G protein that relays signals into the cell, eventually pushing the cell past the cell cycle restriction point
- Mutant RAS encodes a protein that is always active (produces a constant signal to pass through the cell cycle’s restriction point)
- It is mutated in approx 1/3rd of all malignant neoplasms
What is c-MYC?
An oncogene
- Binds to DNA, stimulates synthesis
- Amplified in neuroblastomas and breast cancer
What is HER-2?
An oncogene
- It encodes a growth factor receptor
- It is over expressed
- Seen in 25% of breast cancers
What is pRb?
A tumour suppressor gene
- It governs passage beyond the R checkpoint (by phosphorylation of pRb)
- A effect in both pRb alleles leads to the cell escaping cell cycle control
How is asbestos exposure associated with the development of tumours?
- Asbestos can form fine dust particles which are like needles
- This can enter the lungs and cause chronic inflammation
- Other carcinogens can also enter the lungs along with asbestos
How can the dye industry be associated with the development of tumours?
- Aromatic amines can be inhaled
- They can be hydroxylated in the liver and conjugated with glucuronic acid
- It can then be deconjugated to its active form in the urinary tract by urinary glucuronidase
- The active form sits in the bladder, and leads to bladder cancer
Why is ulcerative colitis associated with an increased risk of malignancy?
- Associated with an increased risk of colorectal carcinoma
- There is DNA damage and microsatellite instability
- May mask symptoms of cancer
Which cancer is cirrhosis associated with an increased risk of?
Hepatocellular carcinoma
Which cancer is Hashimoto’s thyroidosis associated with an increased risk of?
Thyroid lymphoma
- Very rare complication
Which cancer is chronic atrophic gastritis associated with an increased risk of?
Gastric adenocarcinoma
