Lecture 37: Carcinogenesis: causes of cancer

Question 1

What are Heterocyclic aromatic amines (HAAs)?

Answer 1

HAAs are heat-induced mutagenic agent present in some food products. These can cause single stranded DNA breaks, chromosomal aberrations and DNA adducts in guanine-rich regions.

Question 2

What are Polycyclic aromatic hydrocarbons (PAHs)?

Answer 2

Combustion of organic matter results in the generation of PAHs resulting in the development of breast, skin or lung cancer. Bioactivation of PAHs results in carcinogenesis mediated by cytochrome P450 enzymes

Question 3

What is ultraviolet (UV)?

Answer 3

This agent is implicated in the causation of skin tumours by targeting pyrimidine bases.

Question 4

What is ionizing radiation?

Answer 4

Exposure to ionising radiation induces DNA damage. The carcinogenesis effect promotes the production of reactive oxygenation species resulting in oxidative damage, which can result in single stranded breaks. Direct interaction of electrons with DNA resulting in molecular distortion and double stranded breaks.

Question 5

What is asbestos?

Answer 5

Asbestos is found in industry and household applications. Damage occurs through oxidative stress, fibrosis and interaction with the mitotic apparatus of dividing cells.

Question 6

What do carcinogens do?

Answer 6

Carcinogens work by interacting with a cell’s DNA and inducing genetic mutations. A carcinogen is a specific chemical or physical agent that has the ability to cause cancer in individuals exposed to that agent.

Question 7

What is a carciongen?

Answer 7

an external agent associated with causing cancer

Question 8

Which organisation classified agents into carcinogen related categories from 1-4?

Answer 8

The International Agency for Research on Cancer (IARC)

Question 9

What does category 1 of the IARC carcinogen list mean?

Answer 9

carcinogenic to humans

Question 10

What does category 2a of the IARC carcinogen list mean?

Answer 10

probably carcinogenic to humans

Question 11

What does category 2b of the IARC carcinogen list mean?

Answer 11

possible carcinogenic to humans

Question 12

What does category 3 of the IARC carcinogen list mean?

Answer 12

carcinogenicity not classifiable

Question 13

What does category 4 of the IARC carcinogen list mean?

Answer 13

probably not carcinogenic

Question 14

Give 3 examples of category 1 carcinogens:

Answer 14

1) tobacco

2) UV light

3) processed meats

Question 15

Give 2 examples of category 2a carcinogens:

Answer 15

1) red meat

2) working night shifts

Question 16

Give 2 examples of category 2b carcinogens:

Answer 16

1) radio frequency

2) gasoline

Question 17

Give 3 examples of category 3 agents listed in the IARC carcinogen list:

Answer 17

1) caffeine

2) cholesterol

3) fluorescent light

Question 18

What is the main general mechanism of carinogenesis?

Answer 18

DNA damage

Question 19

What are heterocyclic aromatic amines?

Answer 19

heat-induced mutagenic agents present in some food products

Question 20

Give 3 ways in which heterocyclic aromatic amines cause DNA damage:

Answer 20

1) single stranded DNA breaks

2) chromosomal aberrations

3) DNA adducts

Question 21

What are DNA adducts?

Answer 21

covalent modifications to DNA due to carcinogens

Question 22

What process generates polycyclic aromatic hydrocarbons?

Answer 22

the combustion of organic matter

Question 23

What enzyme mediates polycyclic aromatic hydrocarbon carcinogenesis?

Answer 23

cytochrome p450

Question 24

What bases does ultraviolet radiation target?

Answer 24

pyrimidine bases (C, T and U)

Question 25

Give 2 ways in which ionising radiation can damage DNA:

Answer 25

1) it promotes free radical production, resulting in oxidative damage, causing single stranded breaks in DNA 2) direct interaction of electrons with DNA results in molecular distortion and double stranded breaks

Question 26

Give 3 ways in which asbestos causes DNA damage:

Answer 26

1) oxidative stress 2) fibrosis 3) negative interactions with the mitotic apparatus of dividing cells

Question 27

Give 6 examples of viral carcinogens:

Answer 27

1) epstien-barr virus 2) hepatitis B and C 3) kaposi sarcoma herpes virus 4) HIV type 1 5) human papillomavirus type 16 6) human T cell lymphotropic virus type 1

Question 28

What cancers is epstein-barr virus associated with? (2)

Answer 28

1) nasopharyngeal carcinomas 2) lymphomas

Question 29

What cancer is hepatitis B and C associated with?

Answer 29

Hepatocellular carcinoma

Question 30

What cancer is kaposi sarcoma herpes virus associated with?

Answer 30

kaposi sarcoma

Question 31

What cancers is HIV type 1 associated with? (3)

Answer 31

1) kaposi sarcoma 2) carcinoma of the conjunctiva, anus and cervix 3) lymphomas

Question 32

What cancers is human papilloma virus (HPV) type 16 associated with?

Answer 32

carcinoma of the cervix, vulva, vagina, penis, anus, oral cavity, oropharynx and tonsil

Question 33

What cancers is human T cell lymphotropic virus type 1 associated with? (2)

Answer 33

1) adult T cell leukaemia 2) lymphoma

Question 34

Give three examples of carnicogenic protozoa:

Answer 34

1) Clonorchis sinensis 2) Opisthorchis viverrine 3) Schistosoma haematobium

Question 35

What cancer is Helicobacter pylori associated with?

Answer 35

non-cardia gastric carcinoma

Question 36

What cancer is Clonorchis sinensis associated with?

Answer 36

cholangiocarcinoma

Question 37

What is cholangiocarcinoma?

Answer 37

Cancer of biliary tract epithelium

Question 38

What cancer is Opisthorchis viverrine associated with?

Answer 38

cholangiocarcinoma

Question 39

What cancer is Schistosoma haematobium associated with?

Answer 39

urinary bladder cancer

Question 40

Describe the initiation process of carcinogenesis:

Answer 40

the carcinogen reaches a cell activating proto-oncogenes, inactivating onco-suppressor genes and anti-metastatic genes

Question 41

Describe the promotion process of carcinogenesis:

Answer 41

the initiated cell develops defects in growth control and programmed cell death as well as a resistance to cytotoxicity allowing for selective clonal expansion, forming a pool of preneoplastic cells

Question 42

Describe the progression process of carcinogenesis:

Answer 42

further genetic changes allow for the preneoplastic cells to become malignant tumours and eventually a cancer invasion

Question 43

What cell cycle proteins drive progression and act as check points?

Answer 43

cyclins

Question 44

What enzyme phosphorylates protein substrates by forming complexes with their relevant cyclins?

Answer 44

cyclin dependent kinases

Question 45

What 2 amino acids do cyclin dependent kinases phosphorylate?

Answer 45

1) serine 2) threonine

Question 46

In which two stages of the cell cycle can cells be halted and removed?

Answer 46

1) between G1 and S 2) between G2 and M

Question 47

What is biotransformation in relation to carcinogenesis?

Answer 47

the deactivation or activation of a carcinogen absorbed and distributed by a tissue

Question 48

Give two examples of geneotoxic carcinogen mechanisms:

Answer 48

1) DNA adductions 2) chromosomal breakages, fusion, deletion, mis-segregation and non-disjunction

Question 49

Give six examples of non-genotoxic carcinogen mechanisms:

Answer 49

1) inflammation 2) immunosuppression 3) reactive oxygen species 4) reactive nitrogen species 5) receptor activation 6) epigenetic silencing

Question 50

Give three methods of epigenetic silencing:

Answer 50

1) DNA methylation 2) histone methylation 3) histone acetylation

Question 51

Give 4 genes associated with breast cancer in women:

Answer 51

1) BRCA1 2) BRCA2 3) ATM 4) BARD1

Question 52

Give 4 genes associated with colorectal cancer, gastric cancer and endometrial cancer:

Answer 52

1) EPCAM 2) MSH2 3 MSH6 4) MLH1

Question 53

Give 2 genes associated with melanoma:

Answer 53

1) BAP1 2) BRCA2

Question 54

Give 6 genes associated with pancreatic and prostate cancer:

Answer 54

1) BRCA1 2) BRCA2 3) ATM 4) MSH2 5) MSH6 6) MLH1