9 Neoplasia 3&4

Question 1

Describe multifactorial nature of neoplasia pathogenesis

Answer 1

Intrinsic factors: Heredity, Age, Sex
Extrinsic factors: Environment (chemicals, radiation, infection) , Behaviour

Question 2

How can overweight/obesity cause cancer

Answer 2

Adipose tissues can produce hormones & inflammatory molecules that contribute to the development of hyperplasia

Question 3

Describe the geographical variations in the incidence of malignant tumours

Answer 3

Geographical regions can either be protective or carcinogenic depending on the type of cancer

E.g.) Japanese migrants to USA; ⬆️breast cancer⬇️gastric cancer

Question 4

Describe the mechanism of Chemical carcinogenesis

Answer 4

1. The presence of an initiator (non-lethal) in a neoplastic clone causes mutation
2. Monoclonal neoplastic proliferation is caused by a promtoer
3. Expansion of a mutated pop.

Question 5

Examples of chemical carcinogens and the common cancers they can cause

Answer 5

2-naphthylamine: seen in dye&cigarettes, Bladder cancer
Benzopyrene: seen in cigarettes
Aflatoxin: seen in fertilisers, Liver cancer
Asbestos: seen in insulators in buildings, Mesothelioma

Question 6

How can a pro-carcinogen be converted into a carcinogen

Answer 6

Cytochrome P450

Question 7

Carcinogens can be…

Answer 7

Both can be an initiator & promoter (tobacco)
OR
Either initiator/promoter

Question 8

Describe the mechanism of carcinogenesis caused by radiation

Answer 8

Alpha/beta practices, gamma rays, X-rays, UV rays can damage
-DNA directly
-Indirectly by generating free radicals

Question 9

Describe the mechanism of carcinogenesis caused by infection

Answer 9

1. Direct effects (e.g.HPV)
2. Indirect effects (e.g.Hep B) ➡️ chronic liver cell injury & regeneration
3. Reduced Immunity (HIV)

Question 10

Describe how HPV (Human Papilloma Virus) can affect genes that control cell growth

Answer 10

Associated with cervical carcinoma
-HPV makes 2 proteins (E6 & E7)

1. Virus infects cell, causes further replication of virus particles without killing the cell
   Method: E6 inhibit p53 which prevents cell from undergoing apoptosis
2. Interfering with Retinoblastoma protein which is important as a cell cycle checkpoint

Question 11

Describe the functions of Proto-oncogenes
Give an example

Answer 11

Participate in signalling pathways that drive proliferation
-mutations that activate these cause an excessive increase in one/more normal functions

‘Gain-of-function’ mutations

E.g.) RAS

Question 12

What is a RAS gene and how is it involved in neoplasia

Answer 12

-Most common type of abnormality involving proto-oncogenes in human tumours

1. Point mutation in RAS meaning there is no need for a growth factor for RAS to bind to GTP

Question 13

Describe the function of Tumour Suppressor Genes
Give an example

Answer 13

Stop cell proliferation

-in most instances both alleles must be damaged for transformation to occur
-abnormalities in these genes leads to failure of growth inhibition

E.g.) Retinoblastoma, p53

Question 14

Describe the functions of DNA repair genes in neoplasia
Give an example

Answer 14

‘Caretaker genes’
-repairs DNA mutation

Some inherited cancer syndromes have germline mutations that cause malignant neoplasm

E.g.) Xeroderma Pigmentosa (autosomal recessive)
-mutation gene that affects DNA nucleotide excision repair

Question 15

Describe the stages of carcinogenesis

Answer 15

1. Somatic cells are exposed to env. carcinogens that are either initiators/promoters gowing in a monoclonal pop. of mutant genes.
2. Some of the clones harbour mutations affecting a proto-oncogene/tumour suppressor gene, affecting hallmark changes
3. During progression, the cells acquire further activated oncogenes/inactivated tumour suppressor genes
4. This eventually results in a pop. of cells that have acquired a set of mutations that produce all of the hallmarks of cancer

Question 16

Describe the the alterations in growth control required to achieve the stages of carcinogenesis

Question 17

Describe the mechanism by which Retinoblastoma genes causes Retinoblastoma

Answer 17

‘2 hit hypothesis’

1. (40% genetic) Familial Retinoblastoma
   -1 allele present at germline
   -affect both eyes
   -only 1sporadic hit required to develop retinoblastoma
2. (60% random) Sporadic Retinoblastoma
   -no allele present at germline
   -affects one eye
   -LOWER risk of developing retinoblastoma since it requires 2 sporadic hits

Question 18

Identify the tumours that can be inherited and describe the understanding behind this

Answer 18

Xeroderma Pigmentosa:
mutation in one of the genes that affect DNA nucleotide excision repair

Familial breast carcinoma:
BRAC1/BRAC2 genes (involved in repairing double strand DNA breaks

Question 19

Identify medical conditions that are associated with an increased risk of malignancy

Question 20

Occupations associated with the development of tumours

Answer 20

Demolition, asbestos removal workers, Firefighter: risk of breathing in Asbestos causing inflammation & scarring of the lungs
-Mesothelioma

Dye industry: risk of exposure to 2-napthylamine
-Bladder cancer
-Long delay between carcinogen exposure and development of a malignant problem

Question 21

Define Carcinogenesis

Answer 21

Causes of cancer

Question 22

What do initiators and promoters do in neoplasm

Answer 22

Initiator: cause mutation
Promoter: cause sustained proliferation

Question 23

What are the 6 hallmarks of cancer

Answer 23

Relevant to benign & malignant neoplasm:
1. Self-sufficiency in growth signals
2. Resistance to growth stop signals
3. No limit on the no. of times a cell can divide (cell immortalisaiton)
4. Sustained inability to induce new blood vessels (angiogenesis)
5. Resistance to apoptosis

Relevant to ONLY malignant neoplasms:
6. The ability to invade & produce metastases

Question 24

What is Germline mutation
Give examples of this

Answer 24

A detectable variation within the DNA of germ cells (sperm &ova) which can be passed on offspring
e.g.)
-Tumour suppressor genes
-Proto-oncogenes
-Genes which control DNA repair