Neoplasia 2 Flashcards
Revision
What are some causes of cancer?
Inherited predisposition. Chemicals. Radiation. Infections. Inflammation. Lifestyle factors - obesity. Bad luck - unknown cause.
What is an example of Inherited Predisposition?
BRCA gene. Runs in family and makes a person predisposed to have a high likelihood of having breast cancer.
If the chromosomes if the faulty gene is Autosomal dominant what effect does this have and what are some examples of this?
Only need one copy of faulty gene for it to have an effect.
Retinoblastoma. Children with RB mutation have a 10,000 increased risk of RB.
FAP - Familial adenomtous polyposis. APC gene. 100% of bowel cancer before they are 50.
What is the Double Hit Hypothesis and what are some examples of this?
One working gene is enough. 2 faulty copies to have a functional problem. Those who have inherited one faulty copy already are at increased risk. Many of the oncogenes, tumour suppressors etc. we will encounter are associated with cancer syndromes. p53 - Li Fraumeni APC - FAP/Gardener's PTCH - Gorlin's Syndrome PTEN - Cowden's syndrome RET - MEN1 MLHI etc - HNPCC and Muir Torres
What is Chemical Carcinogenesis and what are some examples?
Smoking - >40 carcinogens, polycyclic aromatic hydrocarbons.
Aflatoxin (fungus on peanuts).
Beta-naphthylamine (chemical dyes).
Nitrosamines (food preservative).
Arsenic - skin cancer.
Initiators - long lasting genetic damage. Not sufficient to cause cancer. Must be followed by a promotor.
Promotors - require initiators to have caused damage. Time period can vary after initiation.
Complex.
All seem to cause DNA damage.
Ames’ test.
Seem to cause specific and recurrent genetic alteration based on the chemical involved.
Aflatoxin = p53 mutation.
What is the Glyphosate debate?
Ames’ test negative.
Mixed genotoxicity studies - mainly negative.
One or two studies that suggest it does cause cancer.
No pre-malignant lesions.
Cancers were not reproducible.
But - Monsanto - £226 million pay out.
What is smoking very strongly associated with?
Lung cancer. Very strong association with small cell lung cancer. The worst kind.
Head and neck cancers.
Bladder cancers.
Cervical cancer - with human papillomavirus.
(Increases your chances greatly for all for these).
Over 40 known carcinogens.
Different chemicals appear to have a stronger effect in different organisms.
Where are Polycyclic aromatic hydrocarbons potent?
Potent carcinogen.
Paint it on to the skin = cancer.
Can be present in animal fat from meat.
Smoked meat and fish.
Where do you get aflatoxins, and what are they associated with?
Liver cancers.
From fungus.
Common in china etc. Most liver cancers in china are associated with Hepatitis virus and aflatoxin.
Associated with p53 mutations.
Most liver cancers in the west don’t have p53 abnormality until late cancer stages.
Where do you get Beta Naphthylines from and what are they associated with?
Dye - now heavily regulated.
Very strong association with bladder cancers.
Conjugated in the liver with glucuronic acid and therefore not toxic for long.
Human urine contains glucuronidase - bummer.
What kind of Radiations is associated with Cancer and in what way is it associated with cancer?
UVB (280-320nm).
Causes formation of pyrimidine dimers in DNA.
Nucleotide excision repair (NER) is eventually overwhelmed.
Xeroderma pigmentosa - genetic defect in NER and suffer from numerous skin cancers (inheritance disorder).
CT scans have a much higher dose of radiation of X-rays.
CT scans - large studies have suggested 24% increased risk of cancer after CT scans.
New scanners use a lower dose.
Most are susceptible to leukaemia’s (as in atomic bomb survivors) and thyroid cancers (as in Chernobyl).
How is Microbial Carcinogenesis associated with cancer. What are some examples?
Certain viruses are known to causes cancer.
HPV is associated with tonsil cancer.
E6 (viral oncogene)- increases destruction of p53
E7 (an oncogene product of one of the human papilloma viruses)- prevents retinoblastoma (EB) protein from acting.
Rb usually binds E2F. When free of Rb, E2F promotes transcription of DNA polymerase etc.
The virus doesn’t cause a mutation - indirect effect.
What is EBV and what is it implicated in?
Implicated in several tumours.
Burkitt-lymphoma, B-cell lymphomas, Hodgkin lymphomas, Nasopharyngeal carcinoma.
How can chronic inflammation lead to cancer?
Causes many lymphomas - constant lymphocyte reproduction may lead to errors in production.
Other tumours are caused because the tissue is replicating so often it becomes unstable.
Paraplegic patients with permanent catheters are at risk of developing malignancy.
Stomach - chronic gastritis predisposes to malignant changes.
All of these are often in the context of metaplastic change.
How can Schistosomiasis lead to cancer?
The bugs stay inside you for a long time and cancers are associated with them
