Epidemiological and Environmental Aspects of Cancer (complete)

Question 1

How does epidemiology inform causes for cancers ?

Answer 1

• ~80% of all malignant neoplasms caused by environmental factors
• Show regional differences in cancer rates
• Worldwide differences in rates
• Worldwide differences in cancer rates cannot be attributed to genetic difference only

Question 2

What are the three most common types of cancer (other than skin cancer) among men and women? — aka incidence

Answer 2

Men:

1) Prostate
2) lung/brochus
3) colon/rectum

Women:

1) Breast
2) Lung/bronchus
3) colon/rectum

Question 3

What are the three leading types responsible for cancer mortality for men and women in the US?

Answer 3

Men:

1) lung/bronchus
2) prostate
3) colon/rectum

Women:

1) lung/brochus
2) breast
3) colon/rectum

Question 4

What are 4 groups of environmental carcinogens that have been studied extensively?

Answer 4

1) Polycyclic aromatic hydrocarbons (fossil fuel exhaust – tobacco smoke)
2) Aromatic amines
3) Nitrosamines (produced in your stomach when nitrites are exposed to stomach acid)
4) Aflatoxins

Question 5

Explain how environment chemicals cause cancer, including the importance of activation by microsomal enzymes

Answer 5

• Chemical carcinogens are (mostly) metabolized by microsomal enzymes (e.g. P450) into chemically active forms
• Active form = strong electrophile
• Active forms can modify proteins/RNA/DNA

Question 6

Describe the Ames test

Answer 6

• Measures the ability of a given chemical to mutagenize a specific strain of Salmonella
• This strain has a mutation in a gene required for biosynthesis of histidine (can’t synthesize it!)
• If bacteria are mutagenized, revertants emerge — move away from circle and create a ring around center of plate (capable of growing in absence of histidine)

Question 7

Describe the “principles of carcinogenesis” learned from animal testing of carcinogens

Answer 7

1) Chemical effect is generally dose-dependent
2) A specific carcinogen causes 1 specific type of cancer
3) Carcinogenesis requires time
4) Carcinogenesis requires cell proliferation
5) Tumors represent proliferation of clones of malignant cells
6) Stem cells are at risk to become malignant
7) Malignant cells = stem cells that differentiate abnormally

Question 8

What is the two-step model of carcinogenesis?

Answer 8

1) Initiation (direct effect of carcinogen, irreversible)

2) Promotion: effect of a noncarcinogen, reversible and requires repeated application

Question 9

What is the difference between a carcinogen and tumor promoter?

Answer 9

Promoters promote continual cell proliferation (more than it normally would grow), do not initiate cancer — a type of irritant, cause inflammation

Question 10

What is the evidence that tumor promotion plays a role in development in human cancers

Answer 10

Former smokers (after 14 years) lose their high risk for cancer

Question 11

Explain why cancer is much more common in the elderly compared to young adults

Answer 11

• Elderly have more time to develop genetic damage
• Exposure to more carcinogens/promoters
• Cancers are generally slow in developing — they’ll show up later

Question 12

What is the difference between somatic and germline mutations that cause cancer?

Answer 12

Somatic: mutations that occur in any cell except germ cells — can’t be passed on

Germline: mutations that occur in the germline (sperm, egg) — can be passed on to offspring

Question 13

What are epigenetic factors that cause cancer?

Answer 13

• Carcinogens can covalently modify proteins/RNAs — hypermethylation
• Can disrupt DNA repair