Carcinogens

Question 1

Define carcinogenesis

Answer 1

The process by which normal cells are transformed into cancer cells .

Its a multistep process

It results from accumulation of multiple mutations leading to damaged genes

Nonlethal genetic damage (mutation ) lies at the heart of carcinogenesis (caused by environmental and inherited )

Question 2

Discuss the epidemiology of cancer

Answer 2

> Cancer is the common cause of death especially in the western countries
It accounts for 25% of all death
Major insight into the cause of cancer has been obtained by epidemiologic studies that relate to the environment, hereditary factors, and cultural influences

Question 3

Discuss the causes of cancer

Answer 3

*Cancer is caused by damaged to genes . Commonly carcinogen exposure is involved

Question 4

Discuss the various carcinogenic agents

Answer 4

Carcinogens agents come in various forms and may be seen in any situation eg chemicals, viruses,bacteria,fungi , parasites,ionising and non-ionizing radiation,hormones, and miscellaneous agents

Question 5

How do occupational factors cause cancer?

Answer 5

Various occupations put individuals at risk of exposure to various carcinogens. This increase their likelihood of developing certain cancers

Example :
> Bladder carcinoma: beta-naphthylamine in people employed in rubber industries
> Radiation: Thyroid carcinoma, especially papillary thyroid carcinoma
*Chernobyl in Ukraine radiology

Question 6

How does behavioral?

Answer 6

1. Carcinoma of the cervix (Human papillomavirus ,sexually transmitted )
2. Angiosarcoma of the liver ( Thorotrast ,a contrast medium in diagnostic radiology used between 1930-1950 )
3. Lung carcinoma
   * atmospheric pollutants
   * smoking

Question 7

How do chemical carcinogens cause cancer ?

Answer 7

when a cell is exposed to a chemical, the chemical can initiate damage to the cell. Sometimes the cells can either :

• be repaired
• apoptosis
• damage worsen causing the cell to mutate and proliferate

Question 8

List the chemical carcinoma agents and the kinds of cancers they

Answer 8

Agent / Human cancer sites

>Asbestos /carcinoma of the lung, mesothelioma

Question 9

List the chemical carcinoma agents and the kinds of cancers they

Answer 9

Agent / Human cancer sites
>Asbestos /carcinoma of the lung, mesothelioma

> Benzene / leukaemia ,Hodgkin lymphpma

> Vinyl chloride: Angiosarcoma of the liver

> Aflatoxin B : hepatocellular carcinoma

Question 10

List the chemical carcinoma agents and the kinds of cancers they

Answer 10

Agent / Human cancer sites
>Asbestos /carcinoma of the lung, mesothelioma

> Benzene / leukaemia ,Hodgkin lymphpma

> Vinyl chloride: Angiosarcoma of the liver

> Aflatoxin B: hepatocellular carcinoma

Question 11

How do viral carcinogens cause cancer?

Answer 11

> A large number of RNA and DNA viruses have proven to be oncogenic

Question 12

Which RNA viruses are carcinogenic

Answer 12

• Hepatitis C virus > chronic inflammation > hepatocellular carcinoma
• Human T-cell leukaemia virus type 1(HTLV1) > adult T-cell > lyphoma /leukaemia

Question 13

Which DNA viruses are carcinogenic

Answer 13

• Human papillomavirus
• Epstein -Barr virus
• Hepatitis B virus
• Human herpesvirus 8

Question 14

Which DNA viruses are carcinogenic

Answer 14

• Human papillomavirus
• Epstein -Barr virus
• Hepatitis B virus ( also cause hepatocellular carcinoma )
• Human herpesvirus 8

Question 15

How does Human papillomavirus carcinogens

Answer 15

> High risk eg 16 and 18

• Squamous cell carcinoma of the cervix, anogenital region, and oropharynx
• Integration of viral genome > malignant transformation
• HPV infection initiates an event and additional somatic mutations are needed to complete the carcinogenesis eg smoking, hormonal changes, dietary deficiency

> Low-risk types 6 and 11
causes genital warts

Question 16

How do Epstein Barr virus carcinogens?

Answer 16

• Member of the herpes virus
• Infects epithelial cells of the oropharynx and b lymphocytes > immortalisation of b cells

*It is implicated in the pathogenesis of several human tumors eg burkitt lymphoma ,hodgkin lymphoma( cancer that originates from a type of WBC) and nasopharyngeal carcinoma

Question 17

Oncogenic DNA viruses that are carcinogenic

Answer 17

1. Hepatitis B virus
   * Hepatocellular carcinoma
   * Viral DNA is integrated into the host genome
   * Causes chronic liver injury, regeneration, and cirrhosis
   * Encodes HBx protein which disrupts normal growth control
2. HHV8
   * Kaposi sarcoma
   * Primary effusion lymphoma

Question 18

How is fungi a carcinogen?

Answer 18

> Aflatoxin produced by aspergillus flavus is linked to high incidences of hepatocellular carcinoma

Question 19

How are parasites carcinogens?

Answer 19

> Clonorchis Sinensis (Chinese liver fluke ) causes cholangiocarcinoma

> Schistosoma is strongly implicated in bladder squamous cell carcinoma in Egypt

Question 20

How are bacteria carcinogens ?

Answer 20

1. Helicobacter pylori
   * Major cause of gastritis and peptic ulcer disease. It is implicated in gastric lymphoma (MALT lymphoma )and the treatment of the infection leads to regression of lymphoma. It is also associated with adenocarcinoma

Question 21

List the 4 classes of normal regulatory genes that exist to prevent genetic damage?

Answer 21

1. growth-promoting proto-oncogenes
2. Growth-inhibiting tumor suppressor genes
3. Genes which regulate programmed cell death
4. Genes inc]volved in DNA repair

These all act at various stages of the cell cycle . For a tumor to start, there needs to be a mutation in one of these

Question 22

Essential alteration for carcinogenesis to take place

7 marks

Answer 22

1. Self sufficiency in growth signals - to promotes its own growth
2. Insensitivity to growth inhibitory signals : to overcome growth inhibition
3. Evasion of apoptosis : to avoid cell death
4. Defects in DNA repair : so that repair of mutation does not occur
5. Limitless replicative potential to avoid senescence
6. Sustained angiogenesis
7. Ability to invade and metastasize

Question 23

T/F: A tumor is formed by clonal expansion of a single precursor cell that has incurred genetic damage

Answer 23

True

Question 24

Discuss the multistep pathogenesis of cancer?

Answer 24

> It is a complex process
It is broadly made up of initiating event and promoting event(s)
The initiating event is understood to be an environmental attack causing genetic aberrations and (+- hereditary) and oncogenes are usually involved
Promotion is a series of increasing genetic aberrations > tumor suppressor genes usually involved

Question 25

T/F: Only 2 mutations are needed in oncogenes to transform the cell but 1 mutation is needed in a tumor suppressor gene to transform the cell

Answer 25

False: Only 1 mutation is needed in oncogenes to transform the cell but 2 mutations are needed in a tumor suppressor gene to transform the cell

Question 26

What are oncogenes and what is their role?

Answer 26

* Oncogenes promote cell growth in cancer cells * Derived from normal cellular counterparts called proto-oncogenes * Proto-oncogenes function by regulating cell proliferation and differentiation * Products as growth factors and GF receptors, signal transducers, and nuclear factors * Abnormalities include over and inappropriate expression or structural alterations

Question 27

Give 6 examples of oncogenes?

Answer 27

``` k-ras: pancreatic and colonic adenocarcinomas H-ras: bladder carcinoma N-ras and BRAF: melanoma C-kit: gastrointestinal stromal tumor C-myc : Burkitt lymphoma ```

Question 28

What are tumor suppressor genes

Answer 28

*They are categorised according to their mechanism of action . > Caretaker gene : Maintain the intergrity of the genome by repairing dmage > Gate keepers : Inhibit the proliferation or promote the draeth of cells with damaged dna

Question 29

List the tumor suppressor genes and their function

Answer 29

1.p53: Guardian of the genome because it has 3 critical functions >initiates programs that result in cell arrest by preventing the transition of the cell cycle from G1 to S phase >This allows time for cells to repair damaged DNA > If the DNA damage cannot be repaired,p53 induces the cell to undergo apoptosis 2. Rb1 * Originally described in childhood retinoblast and it regulates the G1-S checkpoint of the cell cycle

Question 30

Genetic predisposition to cancer: If both my parents had cancer will I also suffer the same fate

Answer 30

Even though cancer is a genetic disease, not all cancers are hereditary because some mutations are acquired during a lifetime. Only 10% are hereditary

Question 31

Genetic predisposition to cancer can be divided into 3 categories: list them

Answer 31

1. Autosomal dominant inherited cancer syndrome 2. Defective DNA repair syndrome 3. Familial cancer

Question 32

Discuss the AD inherited cancer syndrome

Answer 32

>Two-hit hypothesis postulated by Knudson > cancer syndrome is Usually due to a point mutation in a single allele of a tumor suppressor gene 2nd mutation occurs in somatic cells > Retinoblastoma *40% familial (AD) (all somatic cells inherit one mutant gene and the second mutation occurs after birth ) *60% sporadic (Both mutations occur after birth ) *Two mutations of the RB locus lead to neoplastic transformation

Question 33

Discuss the familial adenomatous polyposis

Answer 33

>It is an AD inherited cancer syndrome >AD mutation of the APC tumor suppressor gene *Present with numerous colonic adenomas *Develop carcinomas of the colon by age 50 in 100 % of the cases

Question 34

Defective DNA repair syndrome

Answer 34

* Defects in DNA repair results in DNA instability * Autosomal recessive * Examples: hereditary nonpolyposis colon cancer and BRCA 1 and 2 >increaserisk of breast, ovarian, and prostate cancer as well as melanoma

Question 35

Familial cancers

Answer 35

* Higher incidence of cancer in certain families without clearly defined pattern of transmission eg cancer of the colon, breast, ovary, and brain * it occurs at younger age, tumors arising in two or more relatives of the index case and multiple or bilateral tumors