carcinogenesis

Question 1

What is carcinogenesis?

Answer 1

The transformation of normal cells to neoplastic cells through permanent genetic alterations of mutations

Question 2

what is the difference between carcinogenesis and oncogenesis?

Answer 2

carcinogenesis only applies to malignant neoplasms, but oncogenesis applies to benign and malignant neoplasms

Question 3

What is a carcinogen?

Answer 3

agents known or suspected to cause tumours

they act on DNA, i.e. they are mutagenic

Question 4

What percentage of cancer risk is environmental and what percentage is genetic?

Answer 4

85% environmental

15% genetic

Question 5

Why is it difficult to identify the carcinogen that caused a cancer?

Answer 5

1. latent interval may be decades
2. complexity of environment (we are exposed to so many carcinogens)
3. ethical constraints (of directly testing carcinogens on humans)

Question 6

Give examples of cancer that was discovered using epidemiological evidence

Answer 6

1. hepatocellular carcinoma - uncommon in the USA/UK, but common in areas with high Hep B/C and mycotoxins
2. oesophageal carcinoma - high incidence in Japan, China, Turkey and Iran. Gullet cancer in chickens was also observed in the high-incidence area, suggesting the presence of cancer-causing substances in the environment.

Question 7

Give examples of occupational/ behavioural cancer causes

Answer 7

1. lung cancer and smoking
2. bladder cancer and dye and rubber industries, beta-naphthylamine (aromatic amines)
3. scrotal cancer and chimney sweeps due to polycyclic aromatic hydrocarbons

Question 8

Give examples of direct evidence of cancer causation

Answer 8

1. Thorotrast - used as a contrast medium, is a clolloidal suspension of thorium and is irreversibly ingested by phagocytes, causes angiosarcoma
2. chernobyl nuclear reactor explosion - release of radioactive iodine caused increase in thyroid cancer in Ukrainian children

Question 9

Give examples of experimental evidence of cancer causation

Answer 9

1. incidence of tumours in lab animals
2. cell/tissue cultures
3. mutagenecity testing in bacterial cultures

Question 10

Give disadvantages of experimental evidence

Answer 10

1. animals/ cultures may metabolise agents differently to humans
2. bacterial mutation may not mean carcinogenicity in humans

Question 11

State the classes of carcinogens

Answer 11

1. chemical
2. viral
3. ionising and non-ionising radiation
4. hormones
5. parasites
6. mycotoxins
7. miscellaneous

Question 12

What is the name given to the inactive form of a chemical carcinogen and what is this converted to?

Answer 12

pro-carcinogen converted to ultimate carcinogen

Question 13

what chemical can cause lung cancer and what is this due to?

Answer 13

Polycyclic aromatic hydrocarbons due to smoking

Question 14

What chemical can cause skin cancer and what is this due to?

Answer 14

Polycyclic aromatic hydrocarbons due to mineral oils

Question 15

What chemical causes bladder cancer and what is this due to?

Answer 15

beta-naphthylamine, which is an aromatic amine; due to rubber and dye

Question 16

What compound causes gut cancer?

Answer 16

nitrosamines

Question 17

What compound causes leukaemia?

Answer 17

alkylating agents

Question 18

List some chemical compound groups that can cause cancer

Answer 18

1. polycyclic aromatic hydrocarbons
2. aromatic amines
3. nitrosamines
4. alkylating agents

Question 19

Give examples of cancer caused by radiation

Answer 19

1. skin cancer in radiographers
2. lung cancer in uranium miners
3. thyroid cancer in Ukranian children
4. UV light (A or B) causes basal cell carcinoma, melanoma and squamous cell carcinoma and there is increased risk with xeroderma pigmentosum

Question 20

Give examples of biological causes of cancer

Answer 20

hormones, parasites, mycotoxins

Question 21

Give examples of cancer caused by hormones

Answer 21

high oestrogen, increases breast cancer and endometrial cancer

Question 22

Give an example of cancer caused by mycotoxins

Answer 22

hepatocellular carcinoma caused by aflatoxin B1

Question 23

Give examples of cancer caused by parasites

Answer 23

1. Chlonorchis sinensis = cholangiocarcinoma, mutated epithelial cells of bile ducts
2. shistosoma = bladder cancer

Question 24

Give examples of miscellaneous carcinogens

Answer 24

1. asbestos

2. metals (arsenic, chromium, and nickel)

Question 25

Give examples of host factors that contribute cancer

Answer 25

``` race consitutional factors e.g. age, gender, inherited predisposition diet premalignant lesions transplacental exposure ```

Question 26

Give an example of where race plays a role in cancer development

Answer 26

skin cancer in blacks is reduced as they have more melanin

Question 27

Give maples of inherited predispositions that cause cancer

Answer 27

1. familial polyposis coli | 2. retinoblastoma

Question 28

Give examples of pre-malignant conditions that can develop into cancer

Answer 28

colonic polyps cervical dysplasia (CIN) ulcerative colitis undescended testis

Question 29

Give an example of transplacental carcinogenesis

Answer 29

Diethylstiboestrol - DES was shown to cause clear cell carcinoma, a rare vaginal tumor, in girls and women who had been exposed to this drug in utero

Question 30

List ways in which we can identify the cause of cancer

Answer 30

epidemiological evidence occupational/ behavioural direct evidence experimental

Question 31

Give examples of oncogenic viruses

Answer 31

1. Epstein-Barr virus = Burkitt's lymphoma (B cell lymphoma) 2. HPV - cervical cancer, common wart 3. Hep B and C - hepatocellular carcinoma 4. HHV-8 = Kaposi's sarcoma

Question 32

Give reasons why increasing age increases risk of cancer

Answer 32

1. long latent period 2. cumulative risk of exposure to carcinogens 3. accumulations of mutations 4. protective effect of natural killer cells lost with age

Question 33

Give examples of genetic changes that are required to change a cell into a neoplastic cell

Answer 33

1. loss/inactivation of both copies of a tumour suppressor gene (e.g. p53) 2. activation/ abnormal expression of oncogenes 3. telomerase expression

Question 34

Give two roles of a tumour suppressor gene

Answer 34

1. repair DNA damage | 2. inhibits proliferation promotes death of cells (apoptosis) with damaged DNA

Question 35

Give examples of products of oncogenes

Answer 35

growth factor receptor for a growth factor intracellular signalling protein transcription factor