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Explain to a layperson how cigarettes smoke might cause cancer

Explain to a layperson how cigarettes smoke might cause cancer


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I have a very intelligent friend who is a light smoker, and also a Biology layperson.
I wondered whether understanding exactly how cigarettes smoke can cause cancer, might encourage him to smoke less (or quit entirely).

So how would you explain to a Biology layperson how cigarettes smoke might cause cancer?

To clarify, I am looking for a detailed explanation for a layperson, that makes the cause-and-effect much more vivid for them, and thus makes it much more likely that the intelligent layperson would internalize the risks of smoking.

Online resources that I found either gave a too simple answer or concentrated on statistics (which are usually hard for humans to internalize, if I understand correctly).
(Nothing wrong with such explanations, they are just not what I am looking for.)


I encountered the following paragraph in the textbook Life: The Science of Biology:

Some chemicals add groups to the bases. For instance, benzopyrene, a component of cigarette smoke, adds a large chemical group to guanine, making it unavailable for base pairing. When DNA polymerase reaches such a modified guanine, it inserts any one of the four bases at random. Three-fourths of the time the inserted base is not cytosine, and a mutation results.

After finding the following quote in Wikipedia's Benzo(a)pyrene page, I decided to explain specifically how BaP can cause cancer:

BaP has since been identified as a prime carcinogen in cigarette smoke.

My explanation:

  • A protein molecule is a chain of amino acids. Proteins are hugely important, as they are responsible for most of the cellular functions.
  • A DNA molecule is a chain of nucleic acids. There are 4 types of nucleic acids in DNA: A,G,C,T.
  • Having intact DNA molecules is crucial, because they include the encoding of proteins, according to which cells synthesize proteins.
  • A mutation is an alteration of a DNA molecule.
  • A mutation might lead to our cells synthesizing a malfunctioning protein. If a protein that should regulate cell division is malfunctioning, then the result might be uncontrolled cell division - cancer.
  • When you smoke, the chemical BaP (which is found in cigarettes smoke) might alter a G nucleic acid in a DNA molecule in some cell in your body. Later, when this cell tries to divide, it makes a copy of each of its DNA molecules, but it won't be able to identify that G nucleic acid (that BaP altered), so it would put a random nucleic acid in the copied DNA molecule. Thus, there is a 3/4 chance for a mutation.

Secondhand Smoke and Cancer

Secondhand smoke (sometimes called passive smoke, environmental tobacco smoke, or involuntary smoke) is a mixture of sidestream smoke (the smoke from the burning tip of a cigarette or other smoked tobacco product) and mainstream smoke (smoke exhaled by a smoker that is diluted by the surrounding air) (1–3).

Major settings of exposure to secondhand smoke include workplaces, public places such as bars, restaurants and recreational settings, and homes (4). Workplaces and homes are especially important sources of exposure because of the length of time people spend in these settings. The home is a particularly important source of exposure for infants and young children. Children and nonsmoking adults can also be exposed to secondhand smoke in vehicles, where levels of exposure can be high. Exposure levels can also be high in enclosed public places where smoking is allowed, such as restaurants, bars, and casinos, resulting in substantial exposures for both workers and patrons (3).

In the United States, most secondhand smoke comes from cigarettes, followed by pipes, cigars, and other smoked tobacco products.

How is secondhand smoke exposure measured?

Secondhand smoke exposure can be measured by testing indoor air for respirable (breathable) suspended particles (particles small enough to reach the lower airways of the human lung) or individual chemicals such as nicotine or other harmful and potentially harmful constituents of tobacco smoke (3, 5).

Exposure to secondhand smoke can also be evaluated by measuring the level of biomarkers such as cotinine (a byproduct of nicotine metabolism) in a nonsmoker’s blood, saliva, or urine (1). Nicotine, cotinine, and other chemicals present in secondhand smoke have been found in the body fluids of nonsmokers exposed to secondhand smoke.

Does secondhand smoke contain harmful chemicals?

Yes. Many of the harmful chemicals that are in the smoke inhaled by smokers are also found in secondhand smoke (1, 3, 6, 7), including some that cause cancer (1, 3, 7, 8).

Many factors affect which chemicals and how much of them are found in secondhand smoke. These factors include the type of tobacco used in manufacturing a specific product, the chemicals (including flavorings such as menthol) added to the tobacco, the way the tobacco product is smoked, and—for cigarettes, cigars, little cigars, and cigarillos—the material in which the tobacco is wrapped (1–3, 7).

Does secondhand smoke cause cancer?

Yes. The U.S. Environmental Protection Agency, the U.S. National Toxicology Program, the U.S. Surgeon General, and the International Agency for Research on Cancer have all classified secondhand smoke as a known human carcinogen (a cancer-causing agent) (1, 3, 7, 9). In addition, the National Institute for Occupational Safety and Health (NIOSH) has concluded that secondhand smoke is an occupational carcinogen (3).

The Surgeon General estimates that, during 2005-2009, secondhand smoke exposure caused more than 7,300 lung cancer deaths among adult nonsmokers each year (10).

Some research also suggests that secondhand smoke may increase the risk of breast cancer, nasal sinus cavity cancer, and nasopharyngeal cancer in adults (10) and the risk of leukemia, lymphoma, and brain tumors in children (3). Additional research is needed to determine whether a link exists between secondhand smoke exposure and these cancers.

What are the other health effects of exposure to secondhand smoke?

Secondhand smoke is associated with disease and premature death in nonsmoking adults and children (3, 7). Exposure to secondhand smoke irritates the airways and has immediate harmful effects on a person’s heart and blood vessels. It increases the risk of heart disease by about 25 to 30% (3). In the United States, secondhand smoke is estimated to cause nearly 34,000 heart disease deaths each year (10). Exposure to secondhand smoke also increases the risk of stroke by 20 to 30% (10).

Secondhand smoke exposure during pregnancy has been found to cause reduced fertility, pregnancy complications, and poor birth outcomes, including impaired lung development, low birth weight, and preterm delivery (11).

Children exposed to secondhand smoke are at increased risk of sudden infant death syndrome, ear infections, colds, pneumonia, bronchitis, and more severe asthma. Being exposed to secondhand smoke slows the growth of children’s lungs and can cause them to cough, wheeze, and feel breathless (3, 7, 10).

There is no safe level of exposure to secondhand smoke. Even low levels of secondhand smoke can be harmful.

How can you protect yourself and your family from secondhand smoke?

The only way to fully protect nonsmokers from secondhand smoke is to eliminate smoking in indoor workplaces and public places and by creating smokefree policies for personal spaces, including multiunit residential housing. Opening windows, using fans and ventilation systems, and restricting smoking to certain rooms in the home or to certain times of the day does not eliminate exposure to secondhand smoke (3, 4).

Steps you can take to protect yourself and your family include:

  • not allowing smoking in your home
  • not allowing anyone to smoke in your car, even with the windows down
  • making sure the places where your children are cared for are tobacco free
  • teaching children to avoid secondhand smoke
  • seeking out restaurants, bars, and other places that are smokefree (if your state still allows smoking in public areas)
  • protecting your family from secondhand smoke and being a good role model by not smoking or using any other type of tobacco product. For help to quit see smokefree.gov or call 1-877-44U-QUIT.

Do electronic cigarettes emit secondhand smoke?

Electronic cigarettes (also called e-cigarettes, vape pens, vapes, and pod mods) are battery-powered devices designed to heat a liquid, which typically contains nicotine, into an aerosol for inhalation by a user. Following inhalation, the user exhales the aerosol (12).

The use of electronic cigarettes results in exposure to secondhand aerosols (rather than secondhand smoke). Secondhand aerosols contain harmful and potentially harmful substances, including nicotine, heavy metals like lead, volatile organic compounds, and cancer-causing agents. More information about these devices is available on CDC’s Electronic Cigarettes page.

What is being done to reduce nonsmokers’ exposure to secondhand smoke?

On the federal level, several policies restricting smoking in public places have been implemented. Federal law prohibits smoking on airline flights, interstate buses, and most trains. Smoking is also prohibited in most federal buildings by Executive Order 13058 of 1997. The Pro-Children Act of 1994 prohibits smoking in facilities that routinely provide federally funded services to children. The Department of Housing and Urban Development published a final rule in December 2016, which was fully implemented in July 2018, that prohibits the use of cigarettes, cigars, pipes, and hookah (waterpipes) in public housing authorities, including all living units, indoor common areas, and administrative offices, as well as outdoor areas within 25 feet of buildings.

Many state and local governments have enacted laws that prohibit smoking in workplaces and public places, including restaurants, bars, schools, hospitals, airports, bus terminals, parks, and beaches. These smokefree policies have substantially decreased exposure to secondhand smoke in many U.S. workplaces (13). More than half of all states have implemented comprehensive smokefree laws that prohibit smoking in indoor areas of workplaces, restaurants, and bars, and some states and communities also have enacted laws regulating smoking in multi-unit housing and cars (14). The American Nonsmokers' Rights Foundation provides a list of state and local smokefree air policies.

To highlight the health risks from secondhand smoke, the National Cancer Institute requires that meetings and conferences organized or primarily sponsored by NCI be held in a state, county, city, or town that has adopted a comprehensive smokefree policy, unless specific circumstances justify an exception to this policy.

Healthy People 2020, a comprehensive nationwide health promotion and disease prevention framework established by the U.S. Department of Health and Human Services (HHS), includes several objectives addressing the goal of reducing illness, disability, and death caused by tobacco use and secondhand smoke exposure. For 2020, the Healthy People goal is to reduce the proportion of nonsmokers exposed to secondhand smoke by 10%. To assist with achieving this goal, Healthy People 2020 includes ideas for community interventions, such as encouraging the introduction of smokefree policies in all workplaces and other public gathering places, such as public parks, sporting arenas, and beaches.

Because of these policies and other actions, the percentage of nonsmokers who are exposed to secondhand smoke declined from 52.5% during 1999–2000 to 25.3% during 2011–2014 (15). Exposure to secondhand smoke declined among all population subgroups, but disparities still exist. During 2011–2014, 38% of children ages 3–11 years, 50% of non-Hispanic blacks, 48% of people living below the poverty level, and 39% of people living in rental housing were exposed to secondhand smoke (15).

Selected References

National Toxicology Program. Tobacco-Related Exposures. In: Report on Carcinogens. Fourteenth Edition. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 2016.

International Agency for Research on Cancer. Tobacco smoking, Second-hand tobacco smoke, and Smokeless tobacco. In: Personal Habits and Indoor Combustions: A Review of Human Carcinogens. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 100E. Lyon, France: International Agency for Research on Cancer 2012. p. 43-318.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

National Cancer Institute. Cancer Trends Progress Report. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health 2018.

U.S. Food and Drug Administration. Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke: Established List. Silver Spring, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Tobacco Products 2012.

Rodgman A, Perfetti TA. Tobacco and/or tobacco smoke components used as tobacco ingredients. In: The Chemical Components of Tobacco and Tobacco Smoke. Boca Raton, FL: CRC Press 2009. p. 1259.

U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010.

National Cancer Institute. Health Effects of Exposure to Environmental Tobacco Smoke. Smoking and Tobacco Control Monograph 10. NIH Pub. No. 99-4645. Bethesda, MD: U.S. Department of Health and Human Services, National Cancer Institute 1999.

U.S. Environmental Protection Agency. Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. Washington, DC: U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Office of Research and Development 1992.

U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, 2014. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.

National Cancer Institute. A Socioecological Approach to Addressing Tobacco-Related Health Disparities. National Cancer Institute Tobacco Control Monograph 22. NIH Pub. No. 17-CA-8035A. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute 2017.

U.S. Department of Health and Human Services. E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health 2016.

National Institute for Occupational Safety and Health. Promoting Health and Preventing Disease and Injury Through Workplace Tobacco Policies. Current Intelligence Bulletin. DHHS (NIOSH) Publication No. 2015-113. U.S. Department of Health and Human Services, Center for Disease Control and Prevention, National Institute for Occupational Safety and Health 2015.

Tynan MA, Holmes CB, Promoff G, et al. State and local comprehensive smoke-free laws for worksites, restaurants, and bars - United States, 2015. MMWR Morbidity and Mortality Weekly Report 2016 65(24):623-626.


Explain to a layperson how cigarettes smoke might cause cancer - Biology

Smoking is one of the major avoidable risk factors of chronic, life-threatening diseases of the gas exchange and circulatory systems.

The smoke from cigarettes contains several substances that affect the gas exchange system and the cardiovascular system. These include:

tar , a mixture of substances including various chemicals that act as carcinogens.
nicotine , an addictive substance that affects the nervous system by binding to receptors on neurones (nerve cells) in the brain and other parts of the body. It increases the release of a neurotransmitter called dopamine in the brain, which gives feelings of pleasure. It increases the release of adrenaline into the blood, which in turn increases breathing rate and heart rate. There is also some evidence that nicotine increases the likelihood of blood clots forming.
CO , which combines irreversibly with Hb, forming carboxyhaemoglobin. This reduces the amount of Hb available to combine with O2, and so reduces the amount of O2 that is transported to body tissues.


Effects of smoking on the gas exchange system

Chronic obstructive pulmonary disease (COPD)

This is a condition in which a person has chronic bronchitis and emphysema. It can be extremely disabling.

Chronic bronchitis

Various components of cigarette smoke, including tar, cause goblet cells to increase mucus production and cilia to beat less strongly. This causes mucus to build up, which may partially block alveoli. This makes gas exchange more difficult, as the diffusion distance between the air in the alveoli and the blood in the capillaries is greater. The mucus may become infected with bacteria, causing bronchitis . Smokers often have chronic (long-lasting) bronchitis.

The mucus stimulates persistent coughing, which can damage the tissues in the walls of the airways, making them stiffer and the airways narrower.

Emphysema

Smoking causes inflammation in the lungs. This involves the presence of increased numbers of white blood cells, some of which secrete chemicals that damage elastic fibres. This makes the alveoli less elastic. They may burst, resulting in larger air spaces. This reduces the surface area available for gas exchange. This is called emphysema. A person with emphysema has shortness of breath, meaning they struggle to breathe as deeply as they need to, especially when exercising.

Lung cancer

Various components of tar can cause changes in the DNA in body cells, including the genes that control cell division, which can cause cancer. These substances are therefore carcinogens . Cancers caused by cigarette smoke are most likely to form in the lungs but may form anywhere in the gas exchange system, and also in other parts of the body. Smoking increases the risk of developing all types of cancer. Symptoms of lung cancer include shortness of breath, a chronic cough - which may
bring up blood - chest pain, fatigue and weight loss.

Effects of smoking on the cardiovascular system

The nicotine and CO in tobacco smoke increase the risk of developing atherosclerosis . Atherosclerosis is a thickening and loss of elasticity in the walls of arteries. It is caused by build-up of plaques in the blood vessel wall. The plaques contain cholesterol and fibres. They produce a rough surface lining the artery, which stimulates the formation of blood clots.

A blood clot may break away from the artery wall and get stuck in a narrow vessel elsewhere in the blood system, for example in the lungs or in the brain. This prevents blood passing through so cells are not supplied with O2 and die. If this happens in the brain it is called a stroke.

The loss of elasticity In an artery or arteriole also makes it more likely that the vessel will burst when high-pressure blood pulses through. This is another cause of stroke.

If atherosclerosis happens in the coronary arteries that supply the heart muscle with oxygenated blood, the person has coronary heart disease (CHD). Parts of the muscle may be unable to function properly as they do not have enough O2 for aerobic respiration. The muscle may die. Eventually, this part of the heart may stop beating, causing a heart attack.


Evidence for effects of smoking on health

There are two ways in which the effects of smoking on health can be investigated.

Epidemiological evidence

This consists of data collected about people's smoking habits and their health. Large numbers of people should be involved in the study. The researchers then look for correlations between smoking and particular diseases. Although this approach does not provide any definite evidence about a causal link between smoking and the disease, it can at least show whether there could be a causal relationship. If we then have physiological evidence to show how smoking might cause the disease, then this adds up to strong evidence that smoking does indeed cause the disease.

Experimental evidence

This consists of carrying out controlled experiments. For example, the independent variable could be whether or not a subject smokes (or how much they smoke) and the dependent variable could be some aspect of physiology. All other variables should be kept constant. This is not possible with humans, as it would be unethical to make people smoke. In the 1960s, dogs and other animals were used in such experiments. The results showed conclusively that smoking tobacco greatly increases the risk of developing lung cancer. Experiments can also be carried out using cells grown in
tissue culture. Exposure of these cells to chemicals found in tar shows that these chemicals can damage DNA.

Preventing and treating CHD

The risk of developing CHD is increased by:

• inheriting particular alleles of genes
• eating a diet rich in saturated fats and cholesterol
• not taking sufficient exercise
• being obese
• smoking

Severe CHD can be treated with a coronary bypass, in which a piece of blood vessel is taken from another part of the body and sewn into place to provide an alternative route for oxygenated blood to flow from the aorta to the heart muscle.

If the heart is damaged beyond repair, either by CHD or other conditions, then the only long-term option may be a heart transplant. The heart must come from a person who has just died (often in an accident) and has a tissue type that is similar to the recipient. Even so, the recipient will still have to take immunosuppressant drugs for the rest of their life, to prevent their immune system from attacking the donor tissues and rejecting the transplant.

Prevention of CHD and other forms of heart disease is clearly much better than having to carry out complex surgery. Lifestyle choices can be made that reduce the risks listed above (apart, of course, from the genes a person has). However, research shows that slightly obese people are more likely to recover well after heart surgery than thinner people.


Smoking and Cancer

Figure (PageIndex<3>): Cigarette smoking by men in the U.S. began to decline in the 1950s, but it wasn&rsquot until the 1970s &mdash roughly 20 years later &mdash that this was reflected by a concomitant decline in lung cancer deaths in men.

One of the main health risks of smoking is cancer, particularly cancer of the lung. Because of the increased risk of lung cancer with smoking, the risk of dying from lung cancer before age 85 is more than 20 times higher for a male smoker than for a male non-smoker. As the rate of smoking increases, so does the rate of lung cancer deaths, although the effects of smoking on lung cancer deaths can take up to 20 years to manifest themselves, as shown in Figure (PageIndex<3>).

Besides lung cancer, several other forms of cancer are also significantly more likely in smokers than non-smokers, including cancers of the kidney, larynx, mouth, lip, tongue, throat, bladder, esophagus, pancreas, and stomach. Unfortunately, many of these cancers have extremely low cure rates.

When you consider the composition of tobacco smoke, it&rsquos not surprising that it increases the risk of cancer. Tobacco smoke contains dozens of chemicals that have been proven to be carcinogens or causes of cancer. Many of these chemicals bind to DNA in a smoker&rsquos cells and may either kill the cells or cause mutations. If the mutations inhibit programmed cell death, the cells can survive to become cancer cells. Some of the most potent carcinogens in tobacco smoke include benzopyrene, acrolein, and nitrosamines. Other carcinogens in tobacco smoke are radioactive isotopes, including lead-210 and polonium-210.


Link between smoking and cancer


The International Agency for Research on Cancer has classed tobacco use as a Group 1 carcinogen (the highest IARC classification) for cancers of the oral cavity, pharynx, oesophagus, stomach, bowel, liver, lung, pancreas, nasal cavity and paranasal sinuses, larynx, uterine, cervix, ovary, urinary, bladder, kidney, ureter and myeloid leukaemia. Ώ] There is accumulating evidence that tobacco use may also be associated with cancer of the breast (in women). Ώ]

There are over 60 established carcinogens in tobacco smoke. Polycyclic aromatic hydrocarbons (PAH), N-nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN), aromatic amines, 1,3-butadiene, benzene, aldehydes, and ethylene oxide are among the most important compounds because of their carcinogenicity and high levels in cigarette smoke. ΐ] Tobacco has been attributed to 13% of all cancers diagnosed in 2010, with lung cancer having the highest number of cases attributable to cancer. Α]

There is convincing evidence that smoking is a cause of 16 cancer types and limited suggestive evidence linking smoking to one other (see Table 1). Ώ] Research has also found smokeless tobacco (such as chewing tobacco and snuff) have a significantly higher risk of cancers of the cavity, oesophagus and pancreas. Ώ]

The risk of developing cancer decreases with increased time since quitting. Β] Γ] Δ] Studies have reported that among current smokers, life expectancy drops by 10 years or more. Δ] Ε] For adults who quit smoking at 25 to 34 years of age, 10 years of life are regained, at 35 to 44, nine years are regained and 45 to 54, six years of life are regained, compared with those who continue to smoke. Ζ]

Given that a number of cancer types associated with tobacco use, such as pancreatic cancer, are often diagnosed at an advanced stage and cannot be prevented through any other known lifestyle changes or interventions, avoiding exposure to tobacco smoke is one of the only measures available to actively reduce individual risk. Ζ] Tobacco use and cancer have a dose-response relationship meaning the more tobacco smoked over time, the greater the risk of developing tobacco-related cancers. Β] Γ] Η] ⎖]


Table 1. IARC levels of evidence for a link between tobacco and different cancer types

Risk factor Sufficient evidence of carcinogenicity Limited evidence of carcinogenicity Evidence suggesting lack of carcinogenicity
Tobacco smoking Oral cavity, pharynx, oesophagus, stomach, bowel, liver, pancreas, nasal cavity and paranasal sinuses, larynx, lung, uterine cervix, ovary, urinary bladder, kidney, ureter, bone marrow (myeloid leukaemia) Female breast Endometrium (postmenopausal), thyroid
Second-hand smoke Lung Larynx, pharynx
Smokeless tobacco Oral cavity, oesophagus, pancreas
Parental smoking (cancer in the offspring) Hepatoblastoma Childhood leukaemia

Smoking and alcohol

Smoking and alcohol together have a synergistic effect on upper gastrointestinal and aero-digestive cancer risk, meaning the combined effects exceed the risk from either alone. ⎗] It has been estimated that over 75% of cancers of the upper aero-digestive tract in developed countries can be attributed to this effect. For example, compared non-smoking non-drinkers, the approximate relative risks for developing mouth and throat cancer are up to seven times greater for those who use tobacco, up to six times greater for those who use alcohol, and 35 times greater for those who are regular heavy users of both tobacco and alcohol. ⎘]

Alcohol has an independent effect on the risk of oral, pharyngeal, laryngeal and oesophageal cancers, but it is its synergistic effect with smoking that is more significant. ⎙]

See the Alcohol chapterof the National Cancer Prevention Policy for more information.

Second-hand smoke

Evidence shows that second-hand smoke causes lung cancer (see Table 2). Ώ] ⎚] ⎛] ⎜] Long-term exposure to second-hand smoke in the home or workplace can elevate lung cancer risk in a non-smoker by 20-30%. ⎛] There is also some limited evidence of a link between second-hand smoke exposure and cancer of the larynx and pharynx (see Table 2). Ώ] ⎚]

Second-hand smoke may also be a risk factor for cancers of the nasal sinus, naso-pharynx, breast, cervix, bladder and kidney. ⎛] Pre- and postnatal exposure to second-hand tobacco smoke may also increase the risk of brain tumours, lymphomas, and acute lymphocytic leukaemia in children. ⎝] ⎞] ⎟]


Tobacco

Overall smoking has dropped, but stepped up prevention is needed for young adults.

Tobacco use is a leading cause of cancer and of death from cancer. People who use tobacco products or who are regularly around environmental tobacco smoke (also called secondhand smoke) have an increased risk of cancer because tobacco products and secondhand smoke have many chemicals that damage DNA.

Tobacco use causes many types of cancer, including cancer of the lung, larynx (voice box), mouth, esophagus, throat, bladder, kidney, liver, stomach, pancreas, colon and rectum, and cervix, as well as acute myeloid leukemia. People who use smokeless tobacco (snuff or chewing tobacco) have increased risks of cancers of the mouth, esophagus, and pancreas.

There is no safe level of tobacco use. People who use any type of tobacco product are strongly urged to quit. People who quit smoking, regardless of their age, have substantial gains in life expectancy compared with those who continue to smoke. Also, quitting smoking at the time of a cancer diagnosis reduces the risk of death.

For more information about the harms of tobacco use, see:

Also, NCI offers free, confidential information about quitting tobacco by phone and online:


Smoking Causes Cancer In Other Organs Along With Lungs

Scientists have figured out that smoking increases the risk of not just lung cancer but 17 types of cancer. This happens because smoking causes cell mutations in different organs of the body. The latest study shows that smoking a pack of cigarettes causes an additional 150 mutations in every lung cell for each year of smoking.

Other organs that get affected, according to the study, included an average of 97 mutations in each cell in the larynx, 39 mutations for the pharynx, 23 mutations for mouth, 18 mutations for bladder and 6 mutations in every cell of the liver, each year.

Cigarette smoking costs a loss of more than 6 million people each year. Cigarettes contain more than 60 carcinogens, all of which accelerate tumor growth by causing mutations in the tumor DNA.

The scientists analyzed somatic mutations which is the alteration of genes causing them to pass on in cell division and DNA methylation in 5,243 genomes for which tobacco smoking is known to increase risk of cancer.

They studied these cancers and compared them with cancers found in nonsmokers, in order to analyze biophysical differences between the two types, focusing on mutational signatures that vary in different cancers.

Smoking is linked with increased mutation burdens of a variety of different mutational signatures which cause the biologically different effects in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens.

Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. However, smoking causes DNA methylation in a limited amount. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation frequency, although clear proof for this mechanism is lacking in some smoking-related cancer types.

Dr Ludmil Alexandrov, first author from Los Alamos National Laboratory, had this to say, “Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking.

With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer.”

Even though it is a remarkable study in its own, it still remains unclear how exactly smoking causes increase in tumors in other parts of the body that are unaffected by smoke. However, this research points out that different mechanisms are at play by which tobacco smoking causes these mutations, depending on the area of the body affected.

Professor David Phillips, an author on the paper and Professor of Environmental Carcinogenesis at King’s College London, believed that the results were quite fascinating as they were a combination of predicted and unexpected theories, and laid out the direct and indirect effects.

The expected result was that mutations caused by direct DNA damage from carcinogens in tobacco were mostly observed in organs that were in direct contact of tobacco smoke such as mouth and lungs.

In contrast, the unexpected or surprising result was that the other cells of the body suffered from indirect damage, as tobacco smoking seems to affect key mechanisms in these cells that in turn cause DNA mutations, which could be why other organs got affected so frequently.

Consistent with the proposition that an increased mutation load caused by tobacco smoke causes an increased cancer risk, the total mutation burden is higher in smokers compared to nonsmokers, specifically in lung adenocarcinoma, larynx, liver and kidney cancers.

However, differences in total mutation frequency were not observed in the other cancer types linked with smoking and in some there were no statistically significant smoking-associated differences in mutation load, mutation signatures or DNA methylation.

The researchers warned that this does not mean that smokers will be safe from acquiring certain cancers and careful deliberation is required when analyzing such findings. Aside from statistical limitations to thoroughly study the invasive effects of cancer, multiple rounds of clonal expansion over many years are required.

Therefore, it is possible that in the normal tissues from which smoking-associated cancer types originate, there are more somatic mutations or differences in methylation in smokers than in nonsmokers that could have been missed by the scientists as these differences become obscured at the start of clonal evolution, as the immune system has not expanded as such to properly detect the tumors.

Further studies should also involve e-cigarette users as a majority of population is switching to them in the hope of quitting smoking. Teenagers and young adults especially are using e-cigarettes as a form of recreation.

If follow-up studies include e-cigarettes and find similar results of accelerated cancer growth, it is hoped that people will be able to quit smoking altogether in any form.


Effects of cigarette smoke on the human airway epithelial cell transcriptome

Cigarette smoke is the major cause of lung cancer, the leading cause of cancer death, and of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. Using high-density gene expression arrays, we describe genes that are normally expressed in a subset of human airway epithelial cells obtained at bronchoscopy (the airway transcriptome), define how cigarette smoking alters the transcriptome, and detail the effects of variables, such as cumulative exposure, age, sex, and race, on cigarette smoke-induced changes in gene expression. We also determine which changes in gene expression are and are not reversible when smoking is discontinued. The persistent altered expression of a subset of genes in former smokers may explain the risk these individuals have for developing lung cancer long after they have discontinued smoking. The use of gene expression profiling to explore the normal biology of a specific subset of cells within a complex organ across a broad spectrum of healthy individuals and to define the reversible and irreversible genetic effects of cigarette smoke on human airway epithelial cells has not been previously reported.

Figures

Clustering of current- and never-smoker…

Clustering of current- and never-smoker samples. Hierarchical clustering of current ( n =…

Multidimensional scaling plot of current-,…

Multidimensional scaling plot of current-, never-, and former-smoker samples. Multidimensional scaling plot of…

Genes irreversibly altered by cigarette…

Genes irreversibly altered by cigarette smoke. Hierarchical clustering plot of 15 of the…


Materials and Methods

Study Subjects.

We conducted a population-based case-control study of risk factors for prostate cancer in middle-aged men, including lifetime history of cigarette smoking. Case patients included Caucasian and African-American male residents of King County in northwestern Washington, 40–64 years old, who were diagnosed with biopsy-proven prostate cancer between January 1, 1993, and December 31, 1996. Eligible cases were identified from the Seattle-Puget Sound SEER cancer registry and included 100% ages < 60 years and a random 75% sample of those who were ages 60–64 years at diagnosis.

A comparison group (n = 703) without a history of prostate cancer was identified through random digit dialing using a clustering factor of five residences/sampling unit (11) . These individuals were male residents of King County, Washington, 40–64 years of age. Controls were frequency matched to case patient by age (same 5-year group) and recruited evenly throughout the ascertainment period of cases.

All study participants signed informed consent for participation. The Fred Hutchinson Cancer Research Center’s Institutional Review Board approved study forms and procedures. Study subjects completed a structured in-person interview administered by a trained male interviewer. The questionnaire addressed the following areas: social and demographic factors physical development, height, weight, and physical activity reproductive history detailed medical history, including history of BPH and prostate cancer screening family structure and cancer history dietary habits, including total dietary fat intake and servings of cruciferous vegetables consumed/week lifetime smoking and alcohol consumption lifetime sexual history and occupational history. Clinical patient data were available from the cancer registry, including tumor grade and stage of disease at diagnosis. A detailed smoking history before reference date (date of diagnosis for cases and a similar assigned date for controls) was collected, including ages at onset and cessation, duration, and dose of cigarette smoking.

Statistical Methods.

ORs were calculated to estimate the association between prostate cancer and the following smoking variables (continuous and categorized): smoking status (nonsmoker, current, former) duration of smoking (1–9, 10–19, 20–29, 30–39, ≥40 years) number of cigarettes smoked/day (1–10, 11–20, 21–30, 31–40, ≥41) total pack-years of smoking (>0–10, 11–20, 21–30, 31–40, >40) years since cessation in former smokers (>0–9, 10–19, 20–29, ≥30 years) and age first smoked (≤15, 16–17, 18–19, ≥20 years). Multivariate logistic regression (12) analysis was used to compute ORs and estimate 95% CIs adjusted for potential confounders such as age, race, family history of prostate cancer, body mass index, history of prostate cancer screening such as PSA testing (ever had a PSA, had a PSA > 1 year before reference date, number of PSA tests within the 5-years before reference date) or digital rectal examination > 1 year before reference date, dietary habits, physical activity, socioeconomic factors, and medical history. Any covariate that produced a change of >5% in the age-adjusted OR for the smoking status-prostate cancer association was included in the final model, i.e., race, family history of prostate cancer in a first-degree relative, history of PSA testing >1 year before reference date, and a history of BPH. To examine if a dose-response relationship existed between smoking and prostate cancer, trend tests were performed using only cases and controls that were exposed to smoking (13) .

To explore the hypothesis that smoking was associated with the development of more aggressive prostate cancer, additional analyses were completed using a polychotomous multivariate regression model (14) . These models compared controls to cases with less aggressive (localized stage and Gleason score ≤ 7) and more aggressive (regional or distant stage disease or Gleason score 8–10) prostate cancer.


The Biology of Smoking and AMD

Ivan J. Suñer , MD
Scott W. Cousins, MD
Durham, N.C.

As age-related macular degenera tion primarily affects the macula, it has a severe impact on many of the basic ac­tivities of daily living such as driving, recognizing faces and reading. Therefore, it robs af­fected in­dividuals of their independence in their retirement years. Fif­teen million people in the United States alone are affected by AMD, and current estimates project this figure to increase by 50 percent by the year 2020. Ap­proximately 1.75 million (10 percent) Am­er­icans have the advanced or late forms of the dis­ease, exudative/wet AMD and geographic atrophy. 1

Epidemiology of Smoking and AMD

AMD is a multifactorial disease with associated age, environmental, sys­tem­ic and genetic factors. Age is the major risk factor in AMD. The prevalence of all forms of AMD increases significantly with age. It affects approximately 17 percent of all individuals between the ages of 55 and 64, and the prevalence rises to approximately 37 percent in those 75 or older. 2 The more ad­vanced, disabling forms (ex­uda­tive/wet and geographic atrophy) affect 1 percent of Cau­casian patients in their 50s, rising to more than 15 percent of those in their 80s. 1

Figure 1. Representative transmission electron micrographs (TEM) of outer retina and choroid in 16-month-old female mice demonstrating dry AMD findings in mice exposed to cigarette smoke or hydroquinone, a major component of cigarette tar. Panel A. TEM of mouse fed high fat diet without exposure to cigarette smoke or hydroquinone specimen shows mild nodular sub-RPE deposits (white arrows) Bruch's membrane and choriocapillaris are normal thickness. Panel B. TEM of mouse fed high-fat diet and exposed to cigarette smoke there are sub-RPE deposits (white arrows) and thickening of Bruch's membrane with accumulation of a homogenous material (white asterisk). Panel C. TEM of mouse fed high-fat diet plus hydroquinone there are thick sub-RPE deposits (white asterisks) and marked thickening of Bruch' s membrane (white arrows).

Cigarette smoking is the single most important modifiable environmental risk factor for development of all forms of AMD. Multiple large, well-controlled, cross-sectional 3-6 and prospective 7,8 studies in the United States, Australia, France and the Neth­erlands have demonstrated a 2.5- to threefold increase in the risk of all forms of AMD in smokers. Of particular interest is an analysis of pooled data from cross-sectional studies carried out in North Am­erica, Eu­rope and Australia. This data shows an es­pecially large disparity between cur­rent and never smokers with a threefold increase in all forms of AMD, 2.5-fold increase in atrophic AMD, and 4.5-fold increase in neovascular AMD 9 ( See Table 1 ).

Figure 2. Representative flatmount preparation (propidium iodide stain) of the posterior pole of 11-month-old mouse eyes 4 weeks after laser treatment. Four laser spots centered on the optic nerve (D) were performed. Panel A. Control group. CNV lesions were small and circular with discrete borders (dotted lines). Panel B. Oral nicotine group. In this example there is coalescence of three laser injuries gives rise to a large CNV complex (dotted lines). Panel C. Oral nicotine and subconjunctival hexamethonium group. A reduction of the severity of CNV lesions can be clearly appreciated with concurrent administration of a nicotine antagonist, hexamethonium. CNV lesions (dotted line) were similar in size to the control.

An important factor, yet difficult to tease out of this association, is the in­fluence of pack years, current smoking status, ex-smoker and passive smoker. A recent study looked at these issues specifically. 10 It demonstrated a strong association between AMD and number of pack years smoked. The odds ratio in patients smoking greater than 40 pack years was 2.75 as compared to nonsmokers the odds ratio was 3.43 for geographic atrophy and 2.49 for choroidal neovascularization. Smoke cessation was associated with decreasing risk, reaching a similar risk to nonsmokers at 20 years of not smoking. Pas­sive smoking was associated with an odds ratio of 1.87.

An interesting observation is the trend towards earlier onset of AMD, including advanced forms, in Asian countries. This has been attributed in large part to the increased rates of smoking and environmental pollutants. 11

Why Study Smoking and AMD?

Despite the wealth of robust epidemiologic evidence associating smoking with AMD, there is a relative dearth of science to support it. Only now are we beginning to study and elucidate pathobiologic mechanisms of this association. This may be partly due to the concept that cigarette smoking is considered purely a modifiable risk factor. In other words, pa­tients with AMD should quit smoking, and, therefore, there is not more to be gained by further pursuing this association on a biologic level. However, studying the effects of smoking on AMD may provide us with insights into the pathobiology of this complex disease process. Furthermore, some of the lessons we learn may translate into therapies for smokers as well as for nonsmokers.

Composition of Cigarette Smoke

Cigarette smoke is a complex mixture of more than 4,000 chemical substances. Selecting which molecules to study within the daunting number of potential candidates is a difficult issue. The agents present in cigarette smoke are generally subdivided into particulate and gaseous phases. 12 The major components of the particulate phase are tar and nicotine, whereas the gas­eous phase is composed primarily of carbon monoxide, carbon dioxide and nitric oxide.

Various proposed mechanisms by which cigarette smoke may cause end-organ damage include direct effects from chemicals in the smoke, immune activation, secondary hypoxia from pulmonary damage, and secondary sequelae from smoking-induced vascular disease.

The exact pathogenesis of drusen remains an unresolved question. One paradigm, "the response to injury" hy­pothesis, proposes that the RPE cell is the target for specific injury stimuli, resulting in deposit accumulation. 13

Cigarette smoke tar contains nu­merous pro-oxidant compounds within the quinone family. 14 Within these, hydroquinone, a benzene derivative, is the most abundant quinone in cigarette tar. High levels are detected in the plasma and urine of smokers. 14

Our group tested this hypothesis in cultured human RPE cells. In­cu­bation of RPE cells with hydroqui­none induced a specific injury re­sponse called nonlethal blebbing, a process that is proposed to be related to sub-RPE deposit formation. 15 Fur­thermore, exposure to hydroquinone also resulted in decreased levels of matrix metalloproteinase-2 and in­creased levels of collagen IV as measured by zymography ( Suñer I, et al. In­vest Ophthalmol Vis Sci. 200445: ARVO E-Abstract 1810 ). This leads to a net decrease in extracellular matrix turnover, which would result in thickening of Bruch's membrane or formation of sub-RPE deposits.

This relationship was further studied in an animal model by exposing mice to whole cigarette smoke or oral hydroquinone. In mice fed a high-fat diet and exposed to either cigarette smoke in a smoking chamber or di­et­ary hydroquinone, Bruch's membrane was thickened and sub-RPE deposits developed in contrast to controls only receiving a high-fat diet ( See Figure 1 ). 16 Therefore, smoke-related oxi­dants, specifically tar, ap­pear to be a significant oxidative in­jury stimulus that leads to dry AMD in the context of other oxidative sources such as high-fat diet or blue light. It is also likely that while tar is a po­tent oxidant within cigarette smoke, it is not the only oxidant molecule in this pathway.

Nicotine is an attractive candidate molecule to explain an association of smoking with wet AMD. It has been shown to be mitogenic for vascular endothelial cells and smooth muscle pericytes, to reduce apoptosis of vascular endothelial cells, and to induce the formation of capillary tubes. 17,18

We explored the effects of nicotine in a laser model for CNV in mice. We compared CNV size in those receiving nicotine in the drinking water or cigarette smoke in a smoking chamber with control animals. Mice receiving nicotine or cigarette smoke had a statistically significant increase in CNV size (twice the di­ameter in aged mice). This effect was blocked by subconjunctival coadministration of a nonspecific nicotinic antagonist, hexamethonium ( See Figure 2 ). 17

The experiment was carried one step further, and bone-marrow transplantation was performed within the CNV mouse model. Mice that were exposed to cigarette smoke in a smoking chamber and subsequently had bone marrow ablation followed by bone marrow reconstitution from a control mouse had regression of CNV to control levels. Conversely, a control mouse receiving bone marrow from a cigarette smoke-exposed mouse de­monstrated increased CNV size com­parable to cigarette smoke-ex­posed mice ( Cousins S, et al. Invest Oph­thalmol Vis Sci. 200647:ARVO E-Ab­stract 4172 ). This suggests that bone marrow-derived cells, either endothelial or inflammatory precursor cells, may play a role in establishing or modulating choroidal neovascularization.

Immunohistochemical analysis of CNV in cigarette smoke-exposed or nicotine-exposed mice reveals an in­creased number of macrophages in these lesions as compared to controls. Furthermore, it demonstrated higher le­vels of macrophages expressing TNF-a and COX-2 ( Suñer I, et al. In­vest Ophthalmol Vis Sci. 200647: ARVO E-Abstract 1531 ). These are markers of activated macrophages, which supports current theories of in­flam­matory contributions to the path­ogenesis of AMD.

The immediate clinical implications of these findings are that we must continue to impress upon our patients that smoking is not only a significant risk factor for cancer, heart disease and pulmonary disease, but that it is the leading modifiable risk factor for the leading cause of blindness in pa­tients older than 50 years of age. It appears that risks correlate with total number of pack years, and that smoke cessation may result in risk reduction to that of never smokers at 20 years. Fur­thermore, second hand smoke also confers risk for AMD.

Dry AMD patients should be en­couraged to quit smoking. Those with higher-risk lesions per the Age-Re­lated Eye Disease Study should take the recommended vitamin supplementation with the exception of ß-ca­ro­tene, which has been demonstrated to increase rates of lung cancer. 20

Patients with active choroidal neovascularization should be especially encouraged to quit smoking. Fur­thermore, they should abstain from nicotine replacement therapies as nicotine may promote growth of the lesion.

We are entering an era of molecular therapies for retinal diseases. As we learn more about the pathobiologic mechanisms by which smoking im­pacts AMD, we may discover specific pathways of oxidation or im­mu­no­modulation in dry AMD and of vascular endothelial cell and smooth-muscle pericyte proliferation, matrix turnover or immunomodulation that are relevant to wet AMD.

It is also likely that these pathways will be relevant to the biology of AMD not only in smokers, but also nonsmokers. Taking the example of nicotine in wet AMD one step further, it may be that nicotinic receptors (which are also present in nonsmokers) may be a viable target for therapy.

Dr. Suñer is an associate professor of ophthalmology on the Retina Ser­vice at Duke University Eye Center and chief of ophthalmology, Durham Veterans Affairs Medical Center, Dur­­ham, N.C. Contact him at Duke Uni­versity Eye Center, DUMC 3802 Erwin Road, Durham, N.C. 27710, 919-6868-1876 (office), 919-681-6474 (fax), or [email protected]

Dr. Cousins is a professor of ophthalmology and director of the Duke Center for Macular Diseases, Duke Uni­versity Eye Center, Durham, NC. Contact him at Duke University Eye Center, DUMC 3802 Erwin Road, Durham, NC 27710, 919-684-3090 (office), 919-681-6474 (fax), or [email protected]

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