Epidemiology of Cancer and Chemical Carcinogens

Question 1

Understand how epidemiology implicates environmental factors causing most cases of cancer.

Answer 1

More than 80% of all malignant neoplasms are caused by environmental factors, not genetic. Persons who emigrate to different countries or regions change their cancer risk accordingly, a trend which continues through multiple subsequent generations.

Question 2

Know the three most common types of cancer (other than skin cancer) among men and women (incidence), and the three leading types responsible for cancer mortality for men and women (mortality) in the United States.

Answer 2

● Male common types: Prostate, lung, colon.
● Female common types: Breast, lung, colon.
● Male mortality: Lung, prostate, colon.
● Female mortality: Lung, breast, colon.
Note that the death rate for men is almost always higher than the death rate for women– women outlive men with comparable cancers by an average of 8 years. Seems to be partly due to disproportionate infection rates.

Question 3

Explain how environmental chemicals cause cancer and the importance of “activation” by microsomal enzymes.

Answer 3

There are four main groups of carcinogens:
● Polycylic aromatic hydrocarbons (in smoke)
● Aromatic amines (in dyes)
● Nitrosamines (produced in stomach due to amine reaction with ingested food)
● Aflatoxins (produced by Aspergillus fungus, found in contaminated grain).
All of these have to be metabolized by CYP450 enzymes to become carcinogenically active.
CYP450 enzymes are called the ‘microsomal fraction’ of liver enzymes
Once activated, these compounds (electrophilic) react preferentially with proteins, DNA, and RN.
Essentially the compounds need to be oxidized into epoxides before becoming active. Note that not all carcinogens need to
be activated, but vast majority do.

Question 4

Understand the Ames test.

Answer 4

The Ames Test determines the ability of a given chemical to produce mutations.
● Chemical is put in a dish with Salmonella bacteria containing a mutation that makes their growth dependent on histadine
● A microsomal fraction of liver enzymes is added
● The media in the dish has no histadine: bacteria won’t grow w/o a mutation to enable autosynthesis of histadine
● If the chemical is mutagenic, colonies of bacteria that no longer need exogenous histadine to grow begin to arise around the chemical

Question 5

Understand the “principles of carcinogenesis” learned from animal testing of carcinogens. (5)

Answer 5

1. The mutagenic effect of a chemical is generally dose-dependent.
2. A specific carcinogen usually causes one specific kind of neoplasm.
3. Carcinogenesis requires time (years) and cell proliferation (the faster the cells proliferate, the more likely to develop cancer faster).
4. Carcinogenesis occurs mainly in stem cells (fully differentiated cells never become malignant), and carcinogenic changes are transmitted to their daughter cells.
5. These stem cells don’t differentiate normally and develop through two stages:initiation (carcinogenesis, irreversible) and promotion (through continual action of non-carcinogenic promoting agents; reversible).

Question 6

Understand the two-step model of carcinogenesis, and the difference between carcinogen and tumor promoter.

Answer 6

Initiation is the chemical trigger that’s caused by the carcinogen.
Promotion is the ongoing trigger that’s caused by noncarcinogenic chemical factors
Even though a promoter may not be a carcinogen, it can be a promoter of tumorigenesis by promoting cell proliferation.

Question 7

Know the evidence that tumor promotion plays a role in the development of human cancers.

Answer 7

Former smokers lose their high risk for cancer (cigarette smoke contains promoters and pro-inflammatory factors) after 14 years.
Bile salts (promoters) promote cancer in benign colon polyps in rats.

Question 8

Be able to propose an explanation of why cancer is much more common in the elderly compared young adults.

Answer 8

● Acquisition of genetic damage over long periods of time.
● Exposure to more carcinogens and more promoters over long periods of time.
● Cancers are, generally, slow. Makes sense they’d mainly show up later.

Question 9

Understand the difference between somatic and germline mutations that cause cancer, and so-called “epigenetic” factors that cause cancer.

Answer 9

Somatic: Can’t be passed on to offspring
Germline: Can be passed on to offspring
Epigenetic factors: not directly coded for in DNA, but modifications added to proteins or DNA (eg. methylation).
Loss of methyltransferases can activate normally repressed genes.