Neoplasia Lec 2

Question 1

explain the 2 hit hypothesis for tumor suppressor genes

Answer 1

1. Assumption that retinoblastoma requires two mutations
2. Accurately predicts the number of cases of the cancer over time in hereditary and non hereditary retinoblastoma
   –> Originally mathematically based on incidence of retinoblastoma by alfred knudsen in 1971

Question 2

what are the risk factors that increase the cancer risk

Answer 2

age, environmental factors, genetics, inflammation, and viruses

Question 3

explain age and its characteristics

Answer 3

1, Frequently require multiple mutations and often take 20 years or more to develop
2. 2 common causes
–> Accumulation of somatic mutations
–> Decline in immune function

Question 4

explain environmental factors

Answer 4

1. Time required for cancer development decreases with increased mutation rate
   –>Smokers develop lung cancer much faster than non-smokers

Question 5

what are examples of environmental factors

Answer 5

1. Carcinogens
   –> Can induce genetic changes of tumors
   –> Most react with DNA to lead to mutations or DNA damage
   –> Ex:
   —— Mustard gas
   —— N-nitrosos cmpds. In cured meat
   —— Chemotherapy
   —— Benzo9a0pyrene from coal tar or cig smoke
2. UV radiation
3. Ionizing radiation
   –> Ex: x-ray, decay of radioactive isotopes

Question 6

explain genetics

Answer 6

1. Inherited mutations in tumor suppressor genes
2. Many are DNA repair genes

Question 7

what is the function and cancer of the gene mutation BRCA 1/2

Answer 7

• double strand break repair
• ovarian and breast cancer

Question 8

what is the function and cancer of the gene mutation XP (xeroderma pigmentosum)

Answer 8

• nucleotide excision repair
• skin cancer

Question 9

what is the function and cancer of the gene mutation ATM (ataxia telangiectasia)

Answer 9

• double strand break repair
• lymphoma and leukemia

Question 10

what is the function and cancer of the gene mutation BLM (Blooms’ Syndrome)

Answer 10

• DNA helicase
• various

Question 11

describe inflammation

Answer 11

1. Chronic inflammation results in persistent regenerative cell proliferation or hyperplasia and DNA damage by reactive oxygen and nitrogen species produced by immune cells
2. Long unhealed skin wounds characterized by persistent damage can lead to skin cancer
3. Cirrhosis of the liver can lead to hepatocellular carcinoma
4. Chronic gastritis due to long lasting H.pylori infection can lead to gastric cancer
5. Chronic ulcerative colitis can lead to colorectal cancer
6. Villous adenomas (hyperplastic polyps) of the colon can lead to colorectal cancer

Question 12

explain the mechanisms of viruses

Answer 12

1.Integration into the genome (retroviruses) can cause modulation of oncogenes or tumor suppressor genes
2. Chronic inflammation caused by HBV and HCV increases the risk of liver cancer
3. Coral proteins may alter cellular pathways
–> Inactivation of tumor suppressors (ex. E6 in HPV)
–> Disruption of normal cell cycle control

Question 13

what are the 2 types of oncogenic viruses

Answer 13

DNA and RNA

Question 14

describe DNA Viruses

Answer 14

1. EBV (Epstein Barr Virus)
2. KSHV (kaposi’s Sarcoma- Associated Herpesvirus)
3. HPV (Human Papillomaviruses)
4. MCPV (Merkel Cell Polyomavirus)
5. HBV (Hep B Virus)

Question 15

describe RNA viruses

Answer 15

1. HCV (Hep C Virus)
2. HTLV1 (Human T-Cell Lymphotropic Virus Type 1)