The warnings are posted in magazines, newspapers, and on cigarette packages: Smoking Causes Lung Cancer, Heart Disease, Emphysema, and May Complicate Pregnancy. But how do these things happen? What actually causes the Cancer? What about chewing tobacco, cigars, and other forms of tobacco—do they cause cancer too? What is the chance that someone will actually develop cancer if (s)he smokes or uses other forms of tobacco products? Why do some people develop cancer while others don’t?
This next section will explore how the toxic chemicals in tobacco can lead to cancer. The following topics will be explored:
- What is cancer?
- What type of tobacco products cause cancer?
- What compounds in tobacco products cause cancer?
- How do carcinogens in tobacco products actually cause cancer?
- What about nicotine—can it cause cancer?
- Why do most cancers take so long to develop?
- How does genetics play a role in tobacco and cancer?
What is cancer?
Cancer is defined as an abnormal growth of cells in the body that leads to the formation of a large mass of tissue, called a Tumor. Normally, all cells in the body undergo a process of growth and division at some point in time. However, cancer begins when something happens inside the cell that causes them to divide uncontrollably.
Figure 2.1 Cancer cell division. One cell has defective or damaged DNA. This causes it to divide more quickly than healthy cells, resulting in large numbers of cancer cells that form a tumor.
Healthy cells contain specific proteins that signal the cell to stop dividing and growing when no longer necessary. But sometimes, the “stop” signals get corrupted, leading to uncontrolled cell growth and division. The disruption of the stop signals can be caused by genetic, or inherited, defects in the cell’s DNA, or by external dangers such as radiation or environmental toxins, such as pollutants or chemicals, both of which can cause damage to the cell’s DNA. Each of these factors can lead to cancer.
How does cancer spread?
Early in the development of cancer, the abnormal growth of cells begins in one particular location in the body (usually where the cells with DNA damage are located) and produces a tumor. As the tumor grows, tumor cells can break away and enter the bloodstream (Metastasis), where they are then free to travel to any part of the body and continue their rapid and uncontrolled cell growth. People with metastatic cancer often have a lower chance of survival because the cancer has already spread throughout the body. Once cancer begins infecting other regions of the body, it becomes very difficult to completely destroy all of the cancer cells.
As cancer cells reproduce, they begin to deprive normal healthy cells of nutrients, minerals, and chemicals that are essential to their survival. If the normal cells can’t survive, then the function of the organ to which they belong declines, which can lead to illness in the patient. Unfortunately, for many cancer patients, the cancer cells can eventually overtake the normal cells in the body causing death in people who would otherwise still have many years of life left.
Figure 2.2 Tumor growth and metastasis. Cancer cells (green) lead to the formation of a tumor in the tissue of an organ. Some cancer cells can break away from the tumor and enter the bloodstream. Once in the bloodstream, the cancer cells can travel to other areas of the body, causing new tumors to grow (metastasis).
Figure 2.3 Cancer cells spread to the entire body. Once cancer cells enter the bloodstream, they can travel to any region of the body (metastasis). As the cancer cells enter other organs in the body, new tumors may develop.
Use of tobacco products causes many kinds of cancer
Use of tobacco products is one of the most common risk factors for many types of cancers, including cancer of the lung, pancreas, mouth, throat, bladder, liver, stomach, colon, and nose to name a few. Tobacco use is estimated to cause about 30% of all cancer deaths worldwide.
Figure 2.4 Lung cancer risk increases with cigarette use. The graph shows that the risk of lung cancer increases as one increases the number of cigarettes smoked per day. Someone who smokes 5 cigarettes a day has twice the risk of lung cancer compared to a non-smoker, although even a non-smoker has a small risk of lung cancer. [Data from “Understanding Cancer”, National Cancer Institute]
The most common and widely publicized type of cancer from cigarette smoke is lung cancer, which is caused primarily by the inhaled smoke. The risk of lung cancer dramatically increases with the number of cigarettes smoked. Lung cancer is one of the most preventable cancers—it is estimated that 90% of lung cancers are directly related to tobacco products (including both smoke inhaled by the smoker and smoke inhaled by someone in close proximity to the smoker, called Second-hand smoke). Because lung cancer is such a deadly disease, millions of lives worldwide could be saved each year if tobacco products were decreased or even eliminated.
Although tobacco use in the form of cigarette smoking is declining in countries such as the USA, many other countries are experiencing an increase in tobacco use, especially within the poorer countries. In 2008, the World Health Organization predicted that within 2 years, cancer deaths could become the most common form of death in developing countries such as China and India, primarily due to the increased use of tobacco products in these countries. Not only does tobacco contribute to the development of cancer, it also leads to many other types of illnesses, such as addiction, heart disease, stroke, and lung diseases.
What compounds in tobacco products cause cancer?
All tobacco products contain a toxic mixture of dangerous chemicals. For example, just one cigarette contains over 4,800 chemicals, many of which are deadly in large quantities or are known to cause cancer. Chemicals used to make rat poison, arsenic (a type of poison), insecticide, nail polish remover, car batteries, and nuclear weapons are just some of the toxic chemicals found in tobacco products. In fact, these chemicals are found not only in cigarettes, but in all t
ypes of tobacco products, including chewing tobacco, pipes, snuff, cigars, and tobacco lozenges.
Figure 2.6 Toxic chemicals found in cigarettes. This a partial list of some of the toxic chemicals and poisons found in a cigarette and cigarette smoke.
The very fine particles in cigarette smoke (often referred to as “Tar”) contain many harmful ingredients, including 69 known Carcinogens. A carcinogen is a chemical that is known to cause cancer in animals and humans. Most likely, many more carcinogens exist in tobacco than have been identified. Every carcinogen in tobacco has the ability to cause cancer independently from another. Furthermore, the chance of developing cancer increases each time someone is exposed to carcinogens (e.g., each time a cigarette is smoked, or smokeless tobacco is used).
Although not all carcinogens in tobacco products have been yet identified, there are some that are considered the major carcinogens. These include two chemicals—one is called Benzoapyrene, or BaP, and the other is a Nitrosamine called NNK.
BaP is produced by combustion, such as the burning of a cigarette, or the burning of fuel, like that found in automobile or jet plane exhaust. When a cigarette is lit, the burning of the tobacco produces large amounts of BaP in the cigarette smoke. Once in the body, BaP binds directly to DNA within the cell and causes Mutations (changes to the DNA structure). Often times, the DNA mutations can generate “instructions” leading to uncontrolled cell growth and eventual tumor formation.
Although BaP can bind to DNA in any type of cell, it has a tendency to bind more often to DNA in lung cells than other types of cells. We’ll explore all about mutations and cell growth in more detail below.
The other major carcinogen in tobacco is NNK. NNK is produced during the curing (or preservation) process of tobacco. NNK is found in most forms of tobacco, including cigarettes and smokeless tobacco. Scientists have shown that NNK exposure leads to cancer of the lung and the pancreas.
Similar to BaP, NNK binds to DNA in many types of cells and causes DNA mutations. These mutations may lead to the development and growth of cancers. Although NNK can bind to DNA in any type of cell, studies have found that NNK may bind more often to DNA in lung, pancreas, and mouth cells.
Pancreatic cancer is one of worst cancers to develop, as it often carries a death sentence in as little as 5 months. Once it’s detected, very few people survive pancreatic cancer after just 2 years.
How do carcinogens in tobacco products actually cause cancer?
A brief review of DNA
DNA (deoxyribonucleic acid) is the building block of our Genes and chromosomes. DNA is found in every cell within the body and it carries the recipe for building all Proteins that cells use to function properly.
DNA is made up of 4 molecules (also known as Nucleotides or DNA bases). There are over 3 billion of these nucleotides in each cell, and they are packaged to form 23 pairs of chromosomes that reside in the cell’s nucleus. The DNA nucleotides are arranged in a very specific order that contain the “recipe” for each protein to be made.
Think of nucleotides like letters in the alphabet. When letters are arranged in a certain way, they form words that make sense to a reader. This is the same concept for DNA. The nucleotides are arranged in an order that makes sense to the cell. The “words”, which are composed of strings of DNA nucleotides, are called genes. Each gene instructs the synthesis of a particular protein in the cell, with a specific function. So if the order of the nucleotides is changed, then the function of the gene could change, leading to a problem with the resulting protein.
Every cell’s DNA in a person is identical. And surprisingly, each person’s DNA is 99.9% identical to every other human in this world, regardless of their nationality or ethnicity. This 0.1% sequence difference in each person is what makes each person unique.
Figure 2.7 Strands of DNA form genes. DNA is found in every cell in the body. In the cell nucleus, twisted strands of DNA make up the chromosomes. A segment of DNA called a gene instructs the synthesis of specific protein. Proteins do all the work in a cell.
Many cells in the body are constantly dividing and replicating (or reproducing an exact copy). Each time a cell replicates, the DNA replicates as well. Replication of DNA is a critical process of cell replication. Because DNA carries the recipe for making all protein components of the cell, damage to the cell’s DNA could change the entire function of the cell and may also cause problems in cell replication. For example, a cell containing damaged DNA could be replicated indefinitely, producing new copies with damaged DNA.
Figure 2.8 DNA replication. Each of the original strands of DNA is replicated to form an identical copy. One copy of the DNA is found in the newly created cell nucleus and one copy remains in the original cell nucleus.
Cells protect “themselves” from damage to their DNA
The cell has many mechanisms to ensure that each DNA molecule replicates to form an identical copy. In addition, cells contain certain proteins (“spell-checkers” and “proof-readers”) that make sure that there are no “spelling” errors, or mutations in the nucleotide sequence before DNA replication.
Sometimes a mistake happens (meaning a mutation does occur) and the cells produce proteins that “instruct” the cell to actually commit suicide. This form of cell death is called Apoptosis, and it is often the cell’s last resort for making sure that the DNA mutations do not get replicated.
The p53 protein is an example of a protein that instructs cells to undergo apoptosis when spelling errors or mutations in the DNA occur. So p53 comes to the defense–it promotes apoptosis of cells with damaged DNA, thereby eliminating cells that might go on to develop into a cancer.
Despite the help from a “protective” protein like p53, problems can arise. For example, sometimes a mutation can occur in the region of DNA that is responsible for making the “spell-checker” or “proofreader” proteins. In fact, mutations can occur in the p53 gene. Remember that one of the jobs of the p53 protein is to instruct cells to die when mutations are present. So if the p53 gene now has a mutation, the p53 protein can’t do its job to get rid of cells with mutations. Instead, the cells with damaged DNA keep dividing and produce copies of the mutated DNA in the newborn cells. The cycle goes on to produce cancer.
Figure 2.9 The p53 protein directs suicide of cells with DNA damage. Normally the p53 protein helps cells destroy themselves (“suicide”) when their DNA becomes damaged (top row). This prevents the cell from going on to replicate, generating cancer cells. But if the gene for p53 has a mutation, then the p53 protein doesn’t work properly to help the cell commit suicide. Instead, the cells with damaged DNA go on to divide uncontrollably, leading to the development of tumors (bottom row).
Carcinogens damage DNA
Certain chemicals can damage the cell’s DNA and its ability to replicate correctly. These chemicals typically include carcinogens, many of which are found in tobacco products. Carcinogens can bind to DNA to cause mutations. If the mutations occur in genes that normally protect the cell from DNA damage, then the cell begins to replicate, producing more copies of the damaged DNA.
The BaP found in tobacco smoke is a good example of a carcinogen that binds to a segment of DNA for the p53 gene—this is the one that directs cell suicide, or apoptosis. The binding of BaP to the p53 gene causes a mutation in the gene, which can result in the formation of a tumor. Mutations in the p53 gene are found in about 50% of all human cancers, including approximately 60% of lung cancers. Even if BaP was the only carcinogen in smoke, smokers would still have a high risk of developing cancer.
Figure 2.10 Benzo[a]pyrene (BaP) causes lung cancer. Carcinogens from cigarette smoke such as BaP bind to DNA in lung cells. Benzo[a]pyrene binds to the p53 gene segment of DNA, causing a mutation in the p53 gene that leads to lung cancer.
Smokers can damage their DNA tips (telomeres)
Carcinogens in tobacco smoke can cause additional problems for DNA—at the tips. There is a small strand of DNA at the tip of each chromosome called Telomeres. Think of the telomere as the plastic cap on the end of a shoe-lace (chromosome) that keeps it from fraying with wear.
The telomere protects the DNA from damage each time the cell divides, but in the process of every cell division the telomere gets a bit shorter. Once the telomeres reach a certain length, the cells stop dividing, and the DNA remains protected. But if the telomeres get too short, the DNA is no longer protected, thus putting it at increased risk of getting mutations.
The unprotected DNA is another factor that promotes the development of cancer. Additionally, the length of the telomere region may also tell us something about an individual’s health. Healthy young people have long telomeres, but as people age the telomeres get shorter.
Figure 2.11 Telomeres are located on the ends of the chromosomes. These “caps” of DNA protect the DNA from damage each time the cell divides. They get a little shorter with each cell division.
So, what does this have to do with smoking? Scientists have recently discovered that smoking cigarettes causes telomeres to shorten prematurely. While it has always been obvious that smoking cigarettes results in certain signs of premature aging such as wrinkled skin, with new technologies, scientists have found that smokers have shorter telomeres than non-smokers of the same age. Scientists estimate that the length of the smoker’s telomere would be approximately the same length of a non-smoker who is almost 5 years older.
Figure 2.12 Smokers have shortened telomeres. Contrast the chromosomes of a non-smoker (left) and a smoker (right). The shorter telomere of the smoker’s chromosome reflects premature aging of about 5 years, and increases the risk of cancer.
Because of shortened telomeres, smokers have an even greater risk of developing cancer and other diseases. Shortened telomeres could explain, in part, why smokers typically die younger than non-smokers of other age-related diseases, even if they do not get cancer.
National studies have determined that when smoking is started in teenage years and continues into adulthood, the typical smoker’s life span is approximately 8–10 years less than the non-smoker.
- Binding to DNA and producing mutations.
- Shortening the telomeres, putting the DNA at increased risk to develop mutations. It only takes one carcinogen and one mutation to cause cancer.
What about nicotine? Can it cause cancer?
For many years, scientists have debated whether or not nicotine causes cancer. The problem is that no one was actually using nicotine as a drug by itself (without the tobacco) over an extended time period, so there was no way to tell if it was causing cancer in people.
But now scientists have shown that nicotine can cause DNA damage (to cells in the mouth for example) and may help tumors grow larger, especially lung and colon tumors. In addition, nicotine seems to “undo” the benefits of chemotherapy. Chemotherapy is a type of cancer treatment consisting of drugs that kill rapidly dividing cells. Nicotine prevents drugs that are used to treat cancer from killing the lung cancer cells, although scientists are still trying to determine how this happens.
It has been known for a long time that people who undergo chemotherapy to treat their cancer have a poor survival rate if they continue to smoke during the treatment. For patients who are addicted, they might stop smoking during chemotherapy, but decide instead to use a smokeless tobacco product or even a nicotine patch. By doing this, they may be preventing the cancer treatment from working, and suffer the same fate as if they continued to smoke.
Now that nicotine-only products are on the market, it will take a few decades to see if the rate of cancer development in users is similar to that of smokers or oral tobacco users.
Role of Nicotine in Cancer
- May damage DNA
- May contribute to tumor growth
- Prevents chemotherapy drugs from killing cancer cells
Why do most cancers take so long to develop?
Most cancers take years to develop and often occur in people as they get older. This long process is mainly due to the cell’s protective mechanisms to keep cancer from developing. However, as cells age, the chance of accumulating harmful mutations increases and cancer cells can start to grow. Once the cells become cancerous, it can take years of continuous dividing for the cancer cells to produce a human tumor that is large enough to cause illness or migrate to other tissues.
However, the long “incubation” period doesn’t mean that nothing is happening. Every time a tobacco user is exposed to a carcinogen, there is the potential for a mutation to develop in their DNA.
As discussed above, the cell’s protective mechanisms try to get rid of cells with damaged DNA. But as more mutations occur in the DNA, the higher the chance that some of the damaged cells will escape this fate, and then replicate the mutated DNA.
Thus starts the long road to cancer. So although a person who starts to smoke in the teen years may not show any evidence of the disease until much later in life, the teen still has a high risk of accumulating mutations in his/her cellular DNA with each cigarette puff or use of a tobacco product. The more mutations that go undetected in the cells, the higher the chance the damaged cells could lead to cancer.
The earlier a person quits using tobacco, the less likely the person will get cancer later in life. Unfortunately the cancer risk never goes back to pre-smoking levels. But as the body remains free of carcinogens, the cells have more time to repair the damage to their DNA. Thus, tobacco users who quit are at a decreased risk of developing cancer and other tobacco-related diseases compared to those who continue to use tobacco products for the remainder of their life.
How does genetics play a role in tobacco and cancer?
Scientists have known for hundreds of years that certain traits tend to run in families. Children often share similar features with their parents (such as hair color, eye color, height, etc.). It is also well known that certain diseases occur in several members within the same family. But it wasn’t until the 1950’s that researchers discovered how and why traits and diseases run in families. The answer lies in the discovery of DNA.
DNA is the hereditary material in every cell in the body that contains all of the information passed on from parent to child. As researchers learn more about DNA, it is becoming clearer that almost all diseases are due to slight structural changes in DNA. These changes or differences in DNA sequences (variations) between individuals make them more or less likely to develop certain diseases.
Genetics of nicotine addiction and cancer
So what does genetics have to do with smoking? Is the desire to smoke inherited from our parents? Why are some people able to give up tobacco products quickly and while others try to break their habit for their entire lives? What about cancer – why do some people get lung cancer after smoking their entire lives while others do not?
As discussed above, one may inherit a piece of DNA that increases her/his risk of cancer or addiction. In fact, scientists have recently discovered that genetics can play a strong role in nicotine addiction.
Studies have shown that people with certain variations in specific segments of their DNA are more likely to begin smoking, become addicted to nicotine quicker, have a harder time quitting using nicotine products, or are more likely to develop cancer.
Surprisingly, one of the variations in DNA sequence associated with these problems has been located at the gene that makes the nicotinic acetylcholine receptors. As discussed previously, these receptors bind the nicotine, resulting in the cascade of events that leads to nicotine addiction.
The environment is a key factor
However, genetics is not the complete story. For example, just because someone has an altered gene sequence that puts them at increased risk for developing cancer doesn’t mean that the person will get cancer. And, a difference in the gene sequence for the nicotinic acetylcholine receptor in certain individuals doesn’t force someone to take their first puff on a cigarette.
More than likely, it is the environment that someone lives in that determines if (s)he will decide to begin smoking (or using other tobacco products). In this case, the environment refers to peer pressure by friends and family, living with relatives that smoke, exposure to tobacco advertisements, etc.
Thus people may begin smoking based on the environment they live in, but once they start, if they have certain variations in their DNA, it may make it even harder for those people to give up smoking.
Gene tests for addiction and cancer
Currently, there are no genetic tests to determine accurately if one will develop cancer or become addicted to nicotine. These diseases probably result from differences in many genes, not just one gene. So testing for one gene may not be the best predictor.
However, research is just beginning and future findings will likely produce a much clearer picture of how our environment interacts with our DNA. Thus, although scientists are closer to identifying which individuals are at risk of cancer and addiction based on their genetic profile, it is the combination of genetics and how the individual interacts with his/her environment that will be the best predictor of whether the person develops an addiction to nicotine and/or develops cancer.
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