Module 6 Section 4 (Antineoplastics) Flashcards
What is the incidence of cancer?
45% of males and 41% of females will develop cancer at some point in their lives.
In addition, about 30% of all deaths in Canada are due to cancer.
What are the most common types of cancer in Canada?
In Canada, the most common types of cancer are lung, breast, colorectal, and prostate, with lung cancer being the leading cause of cancer death.
Cancer is a generic term for a large number of diseases. However, all cancers share three key features. What are they?
1) Cell growth and division: the ability to proliferate indefinitely. It is important to note that the cell cycle is not faster, but that cell division is continuous and does not stop.
2) Invasion: the ability to invade surrounding normal tissue.
3) Metastasis: the ability to spread throughout the body.
What is cancer characterized by?
In general, cancer is characterised by a long latent period between the time of exposure and the development of the disease.
What is carcinogenesis? Describe the process of it.
It’s the initiation of cancer.
Carcinogens are inactive chemicals called pro-carcinogens that undergo metabolic activation by drug metabolising enzymes in the body.
- The highly chemically reactive forms (termed the ultimate carcinogens) react irreversibly with a DNA molecule, damaging the DNA.
- If this DNA damage is repaired correctly by the cell, then the DNA returns to as it was, and the cell remains a normal cell.
- However, if the DNA is repaired incorrectly, or is not repaired at all, then permanent DNA damage occurs, causing a change in the chemistry of the gene corresponding to the area of DNA damage.
- This change is perpetuated in subsequent divisions of the cell in which it occurs; in other words, a mutation has been induced.
- The genes affected may be oncogenes or tumour suppressor genes.
- Experimental studies have shown that the cells must divide (cell proliferation) to make the genetic change permanent.
Carcinogenesis is a multistage process with three main steps. What are those?
1) Initiation: initiators are chemical agents that alter genes involved in control of cell division and facilitate the division and proliferation of cells.
- Cancer arises when a single cell accumulates a number of mutations and escapes restraints on cell division.
2) Promotion: the second stage of the process of carcinogenesis that causes an accumulation of initiated cells.
- The agents that work at this step do not damage genes but enhance the growth of all cells, including cancer cells or precursors of cancer cells.
3) Progression: the final step of the cancer process where precursors of cancer cells are further modified genetically and phenotypically.
- Chemicals acting at this stage allow for the rapid growth of tumours once they are established, increasing the malignancy of the tumour.
Carciogen alters genetic message -> stimulation of rapid cell growth -> increase in malignancy
True or false: the type of cancer is determined by the type of cells affected.
True
- Cancer of epithelial cells = carcinoma
- Cancer of connective tissue = sarcoma,
- Cancer of hematopoietic cells (i.e. blood cells) = lymphoma or leukemia (depending on the specific blood cells affected).
Cancer can arise from two main factors. What are they?
Genetics: an individual’s genetic makeup contributes to a variation in response to carcinogens.
- Ex: people who have a condition known as Xeroderma pigmentosumhave a genetically based deficiency in DNA repair. As a result, these people are prone to mutations and therefore have a high incidence of skin cancer.
- Another example is the BRCA genes, which are tumour suppressor genes involved in DNA repair. Women who have BRCA mutations have an increased risk of developing breast cancer.
2) Environmental factors: environmental causes of cancer include all non-genetic elements, such as environmental chemicals, diet, and infections.
- These factors are modifiable, meaning a person can decrease the risk of exposure to detrimental environmental factors.
How does smoking cause cancer?
Smoking causes cancer of the lung, upper respiratory tract, esophagus, bladder, and pancreas.
- Smoking may also play a role in other cancers.
The probability of smoking causing cancer increases with increased tar content of cigarettes, increased frequency of smoking, and increased duration of smoking (e.g. five years versus twenty years).
In general, smokers are 8x more likely to develop lung cancer than are non-smokers.
Passive smoking is also a risk factor for cancer. In fact, more than 800 Canadians who do not smoke die from second-hand smoke every year.
How does diet/obesity lead to cancer?
Saturated animal fat and red meat are strongly linked to cancer of the colon, rectum, and prostate.
In addition, high intake of salt has been linked to stomach and other cancers.
It has been shown that skimping on fresh fruit and vegetables can contribute to the development of many different types of cancer, as it is thought that fruit and vegetables contain constituents that block cancer-inducing chemicals produced in our own bodies.
DNA viruses and bacteria are responsible for inducing some cancers. How does this happen?
Viruses:
- Hepatitis B and Hepatitis C can cause liver cancer. It is estimated that up to 80% of liver cancer globally is caused by hepatitis.
- The human papilloma viruses (HPV), which are sexually transmitted, can cause cancer of the cervix.
- Human immunodeficiency virus (HIV) can cause Kaposi’s sarcoma, a systemic disease that often presents with red to violet skin lesions.
Bacteria:
- Helicobacter pylori, the bacterium responsible for causing stomach ulcers, has also been strongly associated with stomach cancer.
True or false: cancer of the liver is most frequent in Southeast Asia and Central Africa.
True
This is because of the high incidence of hepatitis B infection and contamination of foods by aflatoxin.
True or false: colorectal cancer is more prevalent in North America, Europe, and Australia.
True
This is thought to be associated with a Western diet (i.e. a diet high in saturated fat and low in fibre, fresh fruit, and vegetables).
The only officially recognized way to test a chemical for carcinogenicity is to determine whether it causes cancer in laboratory animals. Such tests require two to three years to conduct and are very costly to perform. Provide an example of one kind of test.
Ames Test:
- It employs a mutant of the bacterium Salmonella typhimurium that has lost the ability to make the amino acid, histidine.
- When this mutant bacterium is maintained in a histidine-free culture medium, it cannot grow. However, the mutant bacterium regains the ability to grow when exposed to mutagenic chemicals that initiate DNA repair mechanisms, fixing the original defect.
- When 174 different known carcinogens were tested by the Ames test, 156 (90%) caused mutations in the bacterial mutant. It was thus deduced that if a chemical causes a mutation in the bacterial system, there is a high likelihood that it will be a carcinogen in animals.
What are the goals of s of population-based cancer screening programs?
1) Detect cancer or precancerous conditions
2) Improve the chance of successful treatment
3) Decrease cancer death rates
