L17 - Neoplasia 3 Flashcards
Neoplasia pathogenesis is multifactoral, it involves a combination of intrinsic host factors and extrinsic environmental factors. Give some examples of each
Intrinsic - heredity/age/sex
Extrinsic - high BMI/low fruit and veg intake/poor CV fitness/tobacco use/alcohol use
Most of the evidence we have that shows that extrinsic factors account for 85% of cancer risk comes from migrant studies. What are the three major categories of extrinsic carcinogens?
Chemical, radiation, infections
Give the name of the industrial carcinogen used in the dye making industry. Give some other chemical carcinogens
2-napthylamine
Polycyclic hydrocarbons/ aromatic amines/ nitrosamines
Malignant neoplasms caused by 2-napthylamine were studies and the studies showed that there is a long delay between carcinogen exposure and malignant onset, that the risk depends on the carcinogen dosage and what?
That there is often organ specificity depending on the type of carcinogen e.g. 2-napthylamin normaly precipitates bladder cancer
What test showed that initiators are mutagens?
The Ames test
Carcinogens that act as both initiators and promoters are termed ‘complete carcinogens’. What is meant by a pro-carcinogen
Chemicals which are only converted to carcinogens through the action of cytochrome P450 enzymes in the liver
Give some examples of carcinogenic radiation
UV light/ionising radiation like X-rays and nuclear radiation
Radiation can damage DNA directly or indirectly through the production of ___ ______
Free radicals
Some infections directly affect genes that control cell growth, whilst others cause chronic damage and regneration which can be carcinogenic. Give two such infections associated with being carcinogenic
HPV/EBV/hepatitis B and C/HIV/helicobacter pylori/parasitic infections
What cancer is HPV strongly linked to?
Cervical carcinoma because it expresses proteins that inhibit P53 (checkpoint activated) and RB protein (inhibits DNA replication) function both of which are important in cell proliferation
How do Hep B, Hep C, bacteria and parasites indirectly cause carcinogenesis?
Chronic damage to associated structures, hepatitis for example causes chronic damage to the liver.
How is HIV carcinogenic?
Icnreases the likelihood of infections and thus carcinogenesis
Briefly explain Knudson’s two hit hypothesis
Familial cancers where the individual already has one germline mutant allele only requires one mutation in the normal functioning allele to cause cancer. Whereas in someone with two wild type alleles, then two ‘hits’ (mutations) are necessary, one in each allele to cause carcinogenesis
Which cancer was studies to get the ‘two hit’ hypoethesis?
Retinoblastoma as it arises familially and sporadically
Only one allele of a proto-oncogene need be activated to favour neoplastic growth whereas ___ alleles of tumour suppressor gene must be inactivated to favour neoplastic growth
Both
Oncogenes are abnormally activated versions of normal genes called __________ which favour neoplastic growth
Proto-oncogenes
The oncogenes ____ is mutated in about a third of all malignant neoplasms. The mutant version encodes a constitutively active protein which causes the cell to surpass the ______ ___ and keep on dividing.
Ras
Restriction point
What is the role of the oncogene c-myc
This is a transcription factor that causes the activation of cyclin-dependent kinases and thus entry into the cell cylce.
What is the oncogene HER 2?
A growth factor receptor, mutant HER 2 is constitutively active favouring the growth of neoplasms
Some inherited cancer synromes have germline mutations that cause malignant neoplasms indirectly by affecting DNA REPAIR (look at this in ESA 1). What does Xeroderma Pigmentosum (XP) specifically affect and what is its inheritance pattern?
Nucleotide excision repair - patients are typically very sensitive to UV damage and get skin cancer at a young age.
Autosomal recessive
What is hereditary non-polyposis colon cancer syndrome associated with affecting?
DNA mismatch repair. Patients often get colon carcinoma. Autosomal dominant
Familial breast carcinomas with associated mutations in BRCA1 and BRCA2 have problems with what kind of repair?
Double strand DNA breaks
What is meant when we say that neoplasms have a ‘genetic instability’?
What specific tumour suprression genes protect against genetic instability?
They have an accelerated mutation rate
Caretaker genes
‘Progression’ is seen in the ‘adenoma-carcinoma sequence’ which details how the accumulation of ______ leads to development of malignancy
mutations
What are the six hallmarks of cancer?
These are the hallmarks exhibited by a fully evolved malignant neoplasm:
1) self-sufficiency in growth signals
2) resistance to growth stop signals
3) immortilisation - No hayflick limit
4) Angiogenesis ability
5) resistance to apoptosis
6) the ability to invade and produce metastases
Give two occupations with associated development of tumours
Dye industry and bladder cancer with 2-Napthylamine
Aspestos exposure and mesothelioma
Give two medical conditions with associated increased risk of malignancy
ulcerative colitis/cirrhosis/Hashimoto’s hypothyrodism/chronic atrophic gastritis
