L17 - Neoplasia 3

Question 1

Neoplasia pathogenesis is multifactoral, it involves a combination of intrinsic host factors and extrinsic environmental factors. Give some examples of each

Answer 1

Intrinsic - heredity/age/sex

Extrinsic - high BMI/low fruit and veg intake/poor CV fitness/tobacco use/alcohol use

Question 2

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?

Answer 2

Chemical, radiation, infections

Question 3

Give the name of the industrial carcinogen used in the dye making industry. Give some other chemical carcinogens

Answer 3

2-napthylamine

Polycyclic hydrocarbons/ aromatic amines/ nitrosamines

Question 4

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?

Answer 4

That there is often organ specificity depending on the type of carcinogen e.g. 2-napthylamin normaly precipitates bladder cancer

Question 5

What test showed that initiators are mutagens?

Answer 5

The Ames test

Question 6

Carcinogens that act as both initiators and promoters are termed ‘complete carcinogens’. What is meant by a pro-carcinogen

Answer 6

Chemicals which are only converted to carcinogens through the action of cytochrome P450 enzymes in the liver

Question 7

Give some examples of carcinogenic radiation

Answer 7

UV light/ionising radiation like X-rays and nuclear radiation

Question 8

Radiation can damage DNA directly or indirectly through the production of ___ ______

Answer 8

Free radicals

Question 9

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

Answer 9

HPV/EBV/hepatitis B and C/HIV/helicobacter pylori/parasitic infections

Question 10

What cancer is HPV strongly linked to?

Answer 10

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

Question 11

How do Hep B, Hep C, bacteria and parasites indirectly cause carcinogenesis?

Answer 11

Chronic damage to associated structures, hepatitis for example causes chronic damage to the liver.

Question 12

How is HIV carcinogenic?

Answer 12

Icnreases the likelihood of infections and thus carcinogenesis

Question 13

Briefly explain Knudson’s two hit hypothesis

Answer 13

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

Question 14

Which cancer was studies to get the ‘two hit’ hypoethesis?

Answer 14

Retinoblastoma as it arises familially and sporadically

Question 15

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

Answer 15

Both

Question 16

Oncogenes are abnormally activated versions of normal genes called __________ which favour neoplastic growth

Answer 16

Proto-oncogenes

Question 17

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.

Answer 17

Ras

Restriction point

Question 18

What is the role of the oncogene c-myc

Answer 18

This is a transcription factor that causes the activation of cyclin-dependent kinases and thus entry into the cell cylce.

Question 19

What is the oncogene HER 2?

Answer 19

A growth factor receptor, mutant HER 2 is constitutively active favouring the growth of neoplasms

Question 20

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?

Answer 20

Nucleotide excision repair - patients are typically very sensitive to UV damage and get skin cancer at a young age.

Autosomal recessive

Question 21

What is hereditary non-polyposis colon cancer syndrome associated with affecting?

Answer 21

DNA mismatch repair. Patients often get colon carcinoma. Autosomal dominant

Question 22

Familial breast carcinomas with associated mutations in BRCA1 and BRCA2 have problems with what kind of repair?

Answer 22

Double strand DNA breaks

Question 23

What is meant when we say that neoplasms have a ‘genetic instability’?

What specific tumour suprression genes protect against genetic instability?

Answer 23

They have an accelerated mutation rate

Caretaker genes

Question 24

‘Progression’ is seen in the ‘adenoma-carcinoma sequence’ which details how the accumulation of ______ leads to development of malignancy

Answer 24

mutations

Question 25

What are the six hallmarks of cancer?

Answer 25

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

Question 26

Give two occupations with associated development of tumours

Answer 26

Dye industry and bladder cancer with 2-Napthylamine

Aspestos exposure and mesothelioma

Question 27

Give two medical conditions with associated increased risk of malignancy

Answer 27

ulcerative colitis/cirrhosis/Hashimoto’s hypothyrodism/chronic atrophic gastritis