10. Neoplasms

Question 1

What is carcinogenesis?

Answer 1

Causes of cancer.

Question 2

What are some intrinsic causes of neoplasia?

Answer 2

Age, sex, heredity.

Question 3

What are some extrinsic causes of neoplasia?

Answer 3

Environment, lifestyle.

Question 4

What are the five leading behavioural and dietary risks of cancer?

Answer 4

High body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, and alcohol use.

Question 5

What proportion of cancer deaths are due to the five leading behavioural and dietary risks?

Answer 5

30%.

Question 6

What are the three main categories of extrinsic carcinogens?

Answer 6

Chemicals, radiation, and infections.

Question 7

What did malignant neoplasms caused by 2-napthylamine (industrial carcinogen in dye) show?

Answer 7

There is a long delay between carcinogen exposure and malignant neoplasm onset. The risk of cancer depends on the total carcinogen dosage. There is sometimes organ specificity for particular carcinogens

Question 8

What does the Ames test show?

Answer 8

That initiators are mutagens while promoters cause prolonged proliferation in target tissues.

Question 9

What is done in the Ames test?

Answer 9

A strain of bacteria that requires histidine to grow is split into two batches: one has a possible mutagen added then both are placed in media with minimal histidine. After incubation, only the batch with possible mutagen added has a high number of revertants - this suggests the mutagen causes mutations.

Question 10

What is progression?

Answer 10

The process through which a mutant monoclonal collection of cells eventually becomes fully malignant.

Question 11

In what way do neoplasmic cells have a ‘head start’ in germline mutations?

Answer 11

The normal steps of initiation and some promotion can be skipped.

Question 12

What are the classifications of mutagenic chemical carcinogens?

Answer 12

Polycyclic aromatic hydrocarbons, aromatic amines, N-nitroso compounds, alkylating agents, and diverse natural products.

Question 13

How are some pro-carcinogens converted to carcinogens?

Answer 13

By the cytochrome P450 enzymes in the liver.

Question 14

What are complete carcinogens?

Answer 14

Carcinogens that act as both initiators and promoters.

Question 15

What is radiation?

Answer 15

Any type of energy travelling through space.

Question 16

What is the effect of ionising radiation on atoms?

Answer 16

Strips electrons from atoms.

Question 17

What are ionising energy types?

Answer 17

Alpha particles, beta particles, gamma rays, and X rays.

Question 18

What are electromagnetic energy types?

Answer 18

Gamme rays, X rays, and UV rays.

Question 19

What are nuclear energy types?

Answer 19

Alpha particles, beta particles, and gamma rays.

Question 20

What are the two types of damage to DNA from radiation?

Answer 20

Direct damage and indirect damage by generating free radicals.

Question 21

How does radiation damage DNA directly?

Answer 21

Altering bases, single/double strand DNA breaks.

Question 22

How does radiation damage DNA indirectly?

Answer 22

Free radicals.

Question 23

What are some sources of exposure to radiation?

Answer 23

UV - sunlight, ionising - radon, medical tests, or frequent flying.

Question 24

How can infections damage DNA?

Answer 24

Directly or indirectly.

Question 25

How can infection directly damage DNA?

Answer 25

Affect genes that control cell growth.

Question 26

How can infection indirectly damage DNA?

Answer 26

Causing chronic tissue injury, the resulting regeneration acts as a promoter for any pre-existing mutations or causes new mutations from DNA replications errors.

Question 27

Wat type of carcinogen is HPV (human papilloma virus)?

Answer 27

Direct carcinogen.

Question 28

How is HPV a direct carcinogen?

Answer 28

It expresses the E6 and E7 proteins that inhibit p53 and pRB protein function respectively, both of which are important in cell proliferation.

Question 29

What are the roles of p53 and pRB?

Answer 29

To initiate cell apoptosis, when suppressed this means cells unusually survive.

Question 30

What type of carcinogens are Hepatitis B and C viruses?

Answer 30

Indirect carcinogens.

Question 31

How do Hepatitis B and C viruses act as carcinogens?

Answer 31

They cause chronic liver cell injury and regeneration. This leads to increased of mutations.

Question 32

How can helicobactor pylori increase the risk for gastric, cholangio- and bladder carcinomas?

Answer 32

It causes chronic gastric inflammation and parastitic flues cause inflammation in bile ducts and bladder mucosa, so there is increased risk.

Question 33

How does human immunodeficiency virus (HIV) indirectly act as a carcinogen?

Answer 33

It lowers immunity and allows other potentially carcinogenic infections to occur.

Question 34

What pattern of inheritance does retinoblastoma have?

Answer 34

Dominant pattern of inheritance.

Question 35

How was the dominant pattern of inheritance for retinoblastoma discovered?

Answer 35

Retinoblastoma is a childhood disease. A child had theirs removed and went on to have children, all these children then developed retinoblastomas.

Question 36

What is the two hit hypothesis in retinoblastoma? Explain for familial and sporadic retinoblastoma.

Answer 36

For familial cancers, the first hit was delivered through the germline and affected all cells in the body. The second hit is a somatic mutation in one of the 10 million + retinal cells.
For sporadic retinoblastoma, both hits have to be mutations in the somatic cells.

Question 37

What genes inhibit neoplastic growth?

Answer 37

Tumour suppressor genes.

Question 38

How can tumour suppressor genes stop working?

Answer 38

If both alleles are mutated, hence the two hit theory.

Question 39

What genes enhance neoplastic growth?

Answer 39

Oncogenes, which are abnormally activated versions of the normal proto-oncogenes.

Question 40

How is neoplastic growth favoured?

Answer 40

If both tumour suppressor gene alleles have been deactivated or one proto-oncogene has been abnormally activated into oncogenes.

Question 41

What is the RAS proto-oncogene?

Answer 41

It encodes a small G protein that relays signals into the cell that eventually push the cell past the cell cycle restriction point by phosphorylating Rb.

Question 42

How does the RB gene restrain cell proliferation?

Answer 42

By inhibiting passage through the restriction point.

Question 43

What does inactivation of both RB alleles allow?

Answer 43

Unrestrained passage through the restriction point.

Question 44

How can the restriction point of growth control by deregulated?

Answer 44

By the combination of an activated oncogene and an inactivated tumour suppressor gene.

Question 45

What do the types of proto-oncogenes encode?

Answer 45

Growth factors, growth factor receptor, plasma membrane signal transducers, intracellular kinases, transcription factors, cell cycle regulators, or apoptosis regulators.

Question 46

What is xeroderma pigmentosum due to?

Answer 46

Mutations in one of the seven DNA repair genes that affects DNA nucleotide excision repair.

Question 47

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

Answer 47

Colon carcinoma and germline mutations that affect one of several DNA mismatch repair genes.

Question 48

What is familial breast carcinoma associated with?

Answer 48

Mutations in BRCA1 or BRCA2 genes that normally repair double strand DNA breaks.

Question 49

What is genetic instability?

Answer 49

Alterations in genes that account for the accelerated mutation rate found in malignant neoplasms.

Question 50

What are caretaker genes?

Answer 50

Genes that maintain genetic stability, class of tumour suppressor genes.

Question 51

What is an inherited syndrome that affects nucleotide excision repair and by what effect on the genome?

Answer 51

Xeroderma pigmentosa, by nucleotide instability.

Question 52

What is an inherited syndrome that affects mismatch repair and by what effect on the genome?

Answer 52

HNPCC, by microsatellite instability.

Question 53

What is an inherited syndrome that affects double strand break repair and by what effect on the genome?

Answer 53

Breast/ovarian cancer, by chromosomal instability.

Question 54

What is progression?

Answer 54

The steady accumulation of multiple mutations.

Question 55

How does colon carcinoma develop? (Include the genes involved).

Answer 55

Starts as normal epithelium and then APC gene is mutated. This leads to early adenoma/dysplastic crypt. KRAS gene mutation leads to intermediate adenoma. Smad2/4 mutation causes late adenoma, which develops to carcinoma after p53 mutation. Finally, other genetic mutations lead to metastases.

Question 56

What are the three stages of cancer evolution?

Answer 56

Initiation, promotion, and progression.

Question 57

What are the six hallmarks of cancer that fully evolved malignant neoplasms exhibit?

Answer 57

Self-sufficiency in growth signals, resistance to growth stop signals, no limit on the number of times a cell can divide (cell immortalisation), sustained ability to induce new blood vessels (angiogenesis), resistance to apoptosis and the ability to invade and produce metastases.

Question 58

Which hallmark of cancer is exclusive to malignant neoplasms, rather than relevant to benign and malignant neoplasms?

Answer 58

Hallmark 6: ability to invade and produce metastases.

Question 59

What is a simplified cancer pathogenesis?

Answer 59

Somatic cells are exposed to environmental carcinogens that are either initiators or promoters culminating in a monoclonal population of mutant cells. In 5% of cancer inherited mutations in the germ line can be present. Some of these clones harbour mutations affecting a proto-oncogene or tumour suppressor gene, whose protein transcripts play crucial roles in cell signalling pathways affecting hallmark changes. In progression, cells acquire further activated oncogenes or inactivated tumour suppressor genes, some include genetic instability. This eventually results in a population of cells that have acquired a set of mutations that produce all of the hallmarks of cancer.