Lecture 10

Question 1

Define neoplasm and compare and contrast benign and malignant (cancer) tumor features.

Answer 1

Neoplasm = tumor (abnormal growth of cells)

Benign: not dangerous, localized, will not spread to other sites and can be removed, pt survives long term

Malignant: dangerous, destroys other structures, metastasize (via blood or lymph) can lead to earlier death

Tumor is not always a cancer

Question 2

Contrast “localized”, “locally advanced/invasive” and “metastatic” cancer features

Answer 2

Metastatic: breaks apart and travels

Localized: in one place not harming neighbors

Question 3

Name the general cell type from which: i) carcinoma ii) leukemia/lymphoma iii) sarcoma arise.

Answer 3

Carcinoma: malignancy of epithelial cells

Sarcoma: malignancy of mesenchymal cells (soft tissue, connective, bone, vessels)

Lymphoma/leukemia : malignancy of immune cells

Question 4

Use terminology from above to interpret a cancer description, e.g., metastatic breast carcinoma.

Answer 4

Look at image under FOM Lecture 11 LO 10-1

Metastatic Lung Adenocarcinoma

Metastatic: spread from a distant site
Origin
Type of specific pathology:
Adeno: starting from a gland
From epithelial cells

Question 5

Explain generally how DNA damage and multiple mutations lead to cancer.

Answer 5

Live cells proliferate with damaged DNA leading to more mutations

Question 6

Describe the role of the cell cycle in transformation and why cancer cells are considered “immortal”.

Answer 6

-Disruption of normal cell cycling
-Loss of checks and balances

Question 7

b. Describe the role of inherited defects and name 3 external factors that increase cancer risk.

Answer 7

• Inherited defects: predispose you to the “second hit”; makes you genetically more susceptible to getting cancer
• External factors: chemicals, radiation, viruses/bacteria

Question 8

Distinguish familial from sporadic cancers and the ≈ percentage of each; explain whether cancer or cancer risk is inherited in hereditary cancer syndromes.

Answer 8

Inherited Predisposition 5 – 10%

Most are sporadic cancers – acquired

Familial cancers: known genes BRCA 1 and 2, in close related relatives

Cancer risk is inherited

Question 9

List the most common type of cancer(s) associated with each hereditary cancer syndrome and integrate with the DNA Repair lecture to describe the role of:
a. BRCA in DNA repair, and why its loss increases mutation frequency.
b. MutS (MSH) and MutL (MLH) in DNA repair, and why its loss increases mutation frequency.
c. NER in DNA repair, and its loss increases mutation frequency after sun exposure.

Answer 9

a. Breast Cancer
b MMR : mismatch repair
MutS recognizes damage, MutL nicks and takes out ssDNA loops .
c. Skin cancer. NER excises mutated portion. More damage

Question 10

Describe the general effect of ongoing/excessive cell division or inflammation in a tissue or organ on cancer risk and name this type of condition. Predict the type of cancer increased by: i) endometrial hyperplasia, ii) chronic ulcerative colitis, iii) cirrhosis and iv) non-healing skin wounds

Answer 10

Acquired Pre-neoplastic Conditions: Conditions that put people at risk for cancer
- Associated with XS cell division OR inflammation
Examples:
o Endometrial Hyperplasia –> Uterine Carcinoma
o Chronic Ulcerative Colitis –> Bowel Carcinoma
o Cirrhosis –> Liver Cancer
o Chronic non-healing skin wounds –> Skin Cancer

Question 11

Predict the type(s) of cancer whose risk is increased by: i) fatty foods, ii) smoking, iii) human papilloma virus (HPV), and iv) sunlight.

Answer 11

i) fatty foods –> colon cancer
ii) smoking –> lung bladder neck and head
iii) human papilloma virus (HPV) –> head and neck and cervical
iv) sunlight –> basal cell

Question 12

For chemical carcinogenesis:
a. Describe the feature that distinguishes direct from indirect acting agents.

Answer 12

• Require metabolic conversion to carcinogen
Ex: compounds in cigarette smoke, burned animal fats

Question 13

For chemical carcinogenesis:
b. Describe the source of polycyclic aromatic hydrocarbons (PAH) and why they are indirect acting.

Answer 13

Produced: Burning tobacco, animal fats, fossil fuels
Indirect acting agents
Can cause several different kinds of cancer
 Especially lung and bladder
 Characteristic mutational signature in p53

Question 14

For chemical carcinogenesis:
Describe the roles of initiator and promoter in chemical carcinogenesis and why both are needed.

Answer 14

• Initiator: a carcinogen; causes DNA damage
• Promoter: a mitogen; promotes cell division
- Similar to acquired pre-neoplastic conditions
Both required for carcinogenesis

Question 15

For chemical carcinogenesis:
Explain why PAHs are initiators, and name a promoter that interacts with them for head and neck
cancers.

Answer 15

•because they are carcinogens that cause DNA damage, which can lead to cancer
Example: alcohol (head and neck squamous cancers); especially in combo with smoking

Question 16

For chemical carcinogenesis:
Explain why acquired pre-neoplastic conditions play a similar role to promoters in carcinogenesis.

Answer 16

both are associated with/promote excessive cell division

Question 17

Use DNA variations (aka polymorphisms) in metabolizing and detoxifying enzyme genes to explain why individuals can differ in their response to exposure to PAH, and predict if higher or lower
a. Expression of the PAH metabolizing liver P450 enzyme increases lung cancer risk in light smokers.

Answer 17

Cyp1a1 metabolizes PAH –> burning Tobaccos, animal fats

Higher risk for lung cancer in light smokers

Question 18

Use DNA variations (aka polymorphisms) in metabolizing and detoxifying enzyme genes to explain why individuals can differ in their response to exposure to PAH, and predict if higher or lower:
b. Expression of glutathione transferase enzyme increases the risk for lung and bladder cancer in smokers.

Answer 18

Glutathione S-Transferase detoxifies PAH
- Absent in 50% of Caucasians
-higher risk for lung/bladder cancers in smokers

Question 19

For radiation carcinogenesis, describe:
a. 2 sources of ionizing radiation, the DNA damage they cause, and how this can cause mutations.

Answer 19

X-rays, gamma ray cosmic ray

Ionizing is losing electrons leading to chromosomal aberrations

Atomic Bomb, Chernobyl, Sun

Question 20

For radiation carcinogenesis, describe:
b. DNA damage caused by UV radiation, how this can cause mutation, and 2 associated skin cancers.

Answer 20

• Sun (UV radiation)
ex: Squamous cell carcinoma, basal cell carcinoma
-Associated with total cumulative exposure
ex: Melanoma
-Associated with episodic intense exposure

Question 21

For viral carcinogenesis:
a. Name the checkpoint protein inhibited by HPV (human papilloma virus) proteins and explain how it contributes to the risk of cancer in infected cervical cells.

Answer 21

HPV induces transformation, interferes with cell cycle proteins and p53

Speeding up proliferation and removing checkpoints

Question 22

For viral carcinogenesis:
Describe how chronic liver inflammation caused by Hepatitis B and C increases risk of cancer.

Answer 22

Chronic inflammation and scarring of liver (promoter)

Also HBV scpresses viral protein that can activate TFs that contribute to carcinogenesis

Question 23

For viral carcinogenesis:
Name the first bacterium identified as a carcinogen and describe its association with cancer.

Answer 23

H. Pylori – causes peptic ulcers and increases risk of stomach cancers