AVOID CANCER-MAINTAIN YOUR HEALTH IN MODERN LIFE

What Causes Cancer?

Cancer is a complex group of diseases with many possible causes. In this section you can learn more about the known causes of cancer, including genetic factors; lifestyle factors such as tobacco use, diet, and physical activity; certain types of infections; and environmental exposures to different types of chemicals and radiation  

Genetics and Cancer

• Genes are found in every cell of your body, controlling how each cell functions.

• Mutations (changes) in genes, either inherited from your mother and father or from damage that occurred during a person’s life, contribute to the growth and development of cancer.

• Many of the genes that contribute to the development of cancer fall into broad categories, but usually cancer is caused by multiple changes to several different genes.

• Tumor suppressor genes are protective genes. Normally, they suppress (limit) cell growth by monitoring how quickly cells divide into new cells, repairing mismatched DNA (which is often a cause of mutations; see below), and controlling when a cell dies. When a tumor suppressor gene is mutated (from heredity or environmental factors), cells grow uncontrollably and may eventually form a mass called a tumor. BRCA1, BRCA2, and p53 are examples of tumor suppressor genes. Germline mutations in BRCA1 or BRCA2 genes increase a woman’s risk of developing hereditary breast or ovarian cancers. The most commonly mutated gene in people who have cancer is p53. In fact, more than 50% of all cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired mutations. Germline p53 mutations are rare.

• Oncogenes turn a healthy cell into a cancerous cell. HER2 (a specialized protein that controls cancer growth and spread, found on some cancer cells, such as breast and ovarian cancer cells) and the ras family of genes (genes that make proteins involved in cell communication pathways, cell growth, and cell death) are common oncogenes. Mutations in these genes are almost always acquired (not inherited).

• DNA repair genes fix mistakes made when DNA is replicated (copied). If a person has error in a DNA repair gene, these mistakes are not corrected. Mistakes that aren’t fixed become mutations, which may eventually lead to cancer (especially if the mutation occurs in a tumor suppressor gene or oncogene). Mutations in DNA repair genes can be inherited (such as with Lynch syndrome) or acquired. 

About genes

Genes are made up of deoxyribonucleic acid (DNA) and are found in each cell in your body. Genes control how each cell functions, including how quickly it grows, how often it divides, and how long it lives. Researchers estimate that there are 30,000 different genes in each cell.

Genes are located on 46 chromosomes, which are arranged in pairs, which means you have two sets of 23 chromosomes. You inherit one set of chromosomes from your mother and one set from your father. One chromosome in each set of 23 determines whether you are female or male (these are called the X and Y chromosomes). The other 22 chromosome pairs, called autosomes, determine your other physical features.

Genes control how your cells work by making proteins that have specific functions and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the correct function for the cell. All cancers begin when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

About genetic mutations

There are two basic types of genetic mutations: acquired and germline. Acquired mutations are the most common cause of cancer. These mutations occur from damage to genes during a person’s life, and they are not passed from parent to child. Tobacco use, exposure to ultraviolet (UV) radiation (such as sunlight or from tanning beds), viruses, and age can damage genes and cause these mutations. Cancer that occurs because of acquired mutations is called sporadic cancer.

Less commonly, a mutation can be in every cell of a person’s body from birth. These mutations are typically passed from a parent to a child. This is called a germline mutation. Because this type of genetic change is in every cell of the body, including the reproductive sperm cells (in a boy’s body) and egg cells (in a girl’s body), it can be passed from generation to generation. Cancer caused by germline mutations is called inherited cancer, which makes up about 5% to 10% of all cancers.

Mutations and cancer

Mutations happen often, and the human body is normally able to correct most of these changes. Depending on where in the gene the change occurs, a mutation may be beneficial, harmful, or make no difference at all. Therefore, the likelihood of one mutation leading to cancer is small. Usually, it takes multiple mutations over a lifetime to cause cancer. This is why cancer occurs more often in older people, for whom there have been more opportunities for mutations to build up.

Types of genes linked to cancer

Many of the genes that contribute to the development of cancer fall into broad categories:

Despite all that is known about the different ways cancer genes work, many cancers cannot be linked to a specific gene. It is likely that multiple, different genes are involved in the development of cancer. There is also some evidence that genes interact with their environment, further complicating the role of genes in cancer.

In the future, doctors hope to learn more about the role of genetic changes in the development of cancer, which may lead to improvements in finding and treating cancer, as well as predicting a person’s risk of cancer.

Tobacco and Cancer

Tobacco is the single biggest cause of the cancer in the world

Experts agree that tobacco is the single biggest avoidable cause of cancer in the world  Smoking causes over a quarter (28 per cent) of cancer deaths in the UK and nearly one in five cancer cases 

And smoking doesn’t only cause cancer. It also causes tens of thousands of deaths each year in the UK from other conditions, including heart and lung problems  Worldwide, tobacco caused an estimated 5.1 million deaths in 2004 – that’s one every six seconds Around half of all regular smokers will be killed by their habit if they continue to smoke  And half of those will die in middle age, losing between one and two decades of life compared with non-smokers

Smoking causes many different types of cancer

Smoking increases the risk of at least 14 cancers, including cancer of the lung, larynx (voice box) oesophagus (gullet), mouth and pharynx (upper throat), bladder, pancreas, kidney, liver, stomach, bowel, cervix, ovary, nose and sinus as well as some types of leukaemia. There is some evidence that smoking could cause breast cancer

After lung cancer, the upper aerodigestive tract cancers (mouth, upper throat, voice box and gullet) have the highest proportions of cancer cases caused by smoking – population attributable fractions, or PAFs, of more than six 

Smoking greatly increases the risk of lung cancer

More than four in five UK lung cancers are caused by smoking. Lung cancer is the most common cause of cancer death in the UK and accounts for around two thirds (68 per cent) of smoking-related cancer deaths People who smoke were first shown to be more likely to develop lung cancer than non-smokers in 1950 This study found that people who smoked around 20 cigarettes a day had 26 times the lung cancer risk of non-smokers. And people who smoked around three cigarettes a day still had six times the lung cancer risk of non-smokers.After these first results came out, UK scientists began a large long-running study of smoking in British doctors, which Cancer Research UK has helped to fund, that has told us a lot about the dangers of smoking.This study has found similarly huge risks associated with smoking. Men who smoked at  25 or more cigarettes a day had over 24 times the risk of dying from lung cancer as people who had never smoked There are long time lags between changes in the number of people who smoke and the number of people who develop lung cancer due to smoking .So rates of lung cancer in the UK reflect smoking rates decades earlier. 

Lung cancer risks are highest in people who smoke more cigarettes per day, for more years, from a younger age

We cannot exactly calculate a person’s lung cancer risk based on how many cigarettes they smoke or the number of years they have been a smoker. But research has shown that lung cancer risk is greatest among those who smoke the most cigarettes, over the longest period of time, having started at the youngest age Although both have an effect on risk, the number of years someone has spent smoking is more important than the number of cigarettes they smoke a day. This means that overall, smoking 20 cigarettes a day for 20 years is even worse for you than smoking 40 a day for 10 years.

Even light or occasional smoking is bad for your health

Although the risk of an early death increases the more you smoke, people who think of themselves as light or occasional smokers also have an increased risk compared to people who don’t smoke. One study found that people who smoked up to four cigarettes a day were about 50 per cent more likely to die prematurely than non-smokers. And the Million Women study found that women who smoked up to 10 cigarettes a day were twice as likely to die prematurely than non-smokers.  Large studies looking at the health risks of smoking, such as the British Doctors Study and the Million Women Study, have found that people smoking between 1 and 14 cigarettes a day are at least seven times as likely to die from lung cancer than people who have never smoked. And one study found people who smoked between 5 and 9 cigarettes a day had a higher risk of dying from lung cancer, or any type of cancer 20.

Stopping smoking can reduce the risk

A large number of studies have shown that stopping smoking can greatly reduce the risk of smoking-related cancers, compared to continuing to smoke. And the earlier you stop, the better. The latest results from the British Doctors’ Study show that stopping smoking before the age of 30 meant  that life expectancy remained similar to that of a non-smoker. And even people who quit smoking when they were about 60 years old lost fewer years of life to smoking than those who continued.

Cutting down is a good start, but the big benefits come from quitting

The evidence for the health benefits of cutting down the number of cigarettes you smoke is mixed. Some studies have shown that reducing your cigarette consumption, compared to carrying on smoking the same amount, has benefits for lung cancer risk and overall survival. But other studies found benefits only with quitting completely.

However if you reduce the amount you smoke you may be more likely to stop smoking in future. So although you only experience the full health benefits if you stop smoking altogether, cutting down can be a good first step, if you find it too difficult to quit completely in one go.

 Tobacco smoke contains many dangerous chemicals

Scientists have identified over 5,300 different chemicals in tobacco smoke. The International Agency for Research into Cancer (IARC), the gold standard for establishing the causes of cancer, state that there are more than 70 chemicals in tobacco smoke that have been found to cause cancer in studies involving people or in the laboratory. And many of the other thousands of chemicals are toxic and harmful to your health, including carbon monoxide, hydrogen cyanide and ammonia.In 1994 tobacco companies in the US released a list of 599 different cigarette additives, which included chocolate, vanilla, sugar and liquorice as well as common herbs and spices. Although these don’t make cigarettes any more toxic, they are meant to make cigarettes taste nicer and ensure that smokers want to continue smoking. Flavoured tobacco, such as menthol or chocolate-flavoured cigarettes, will be banned in Europe from 2016 under the Tobacco Products Directive. Although additives necessary for manufacturing tobacco can continue to be used, including sugar lost during the curing process, tobacco companies will have to do more research into additives with the possibility that those found to be more harmful or addictive could be banned from use .

Chemicals in tobacco smoke can damage the body in many ways

Chemicals found in tobacco smoke can damage DNA. For example, studies have shown that benzo(a)pyrene damages a gene called p53 that normally protects our cells from cancer. While polonium-210 becomes concentrated in hotspots in smokers’ airways, subjecting them to very high doses of high-energy alpha-radiation that damages the DNA of nearby cells .The cocktail of chemicals in tobacco smoke is even more dangerous as a mix. Toxic metals found in tobacco smoke, like cadmium, arsenic, and lead, stop our cells from repairing DNA damage. This worsens the effects of chemicals like benzo(a)pyrene that damage DNA and makes it even more likely that damaged cells will eventually turn cancerous.Many tobacco poisons disable the cleaning system that our bodies use to remove toxins. Some substances including formaldehyde and acrolein kill cilia, tiny hairs in our airways that help to clear away toxins.

Nicotine is a very addictive drug

Most smokers do not smoke out of choice, but because they are addicted to nicotine. This was highlighted in a report by The Royal College of Physicians into the effects of nicotine. They also compared nicotine to other supposedly ‘harder’ drugs such as heroin and cocaine. They looked at many things including how these drugs cause addiction, how difficult it is to stop using them and how many deaths they caused. The report concluded that nicotine is a highly addictive substance, particularly when people are exposed to it through using tobacco, and that tobacco dependence is at least as serious as addiction to ‘harder’ drugs.People associate smoking with feeling less stressed and anxious, but the evidence suggests this is only because it temporarily relieves the unpleasant symptoms of nicotine withdrawal. If anything, current smokers seem to feel more stressed and anxious than ex-smokers or people who have never smoked.Smokers can also make mental links with abstract things like the smell of cigarettes, objects related to smoking like ashtrays and lighters, and situations in which they usually smoke. These can all act to reinforce the addiction to smoking. 

Smokers are still exposed to dangerous chemicals if they smoke filtered or ‘low-tar’ cigarettes

Current smokers have a higher risk of lung cancer than former smokers or never smokers, whatever type of cigarettes they smoke. There is no difference between the risk of dying from lung cancer for smokers of cigarettes ‘rated’ as medium, low and very low in tar. But smoking unfiltered high tar varieties makes the risk even higher.The amounts of tar or nicotine associated with a particular variety of cigarette are based on machine measurements of smoking. But the measurements don’t accurately reflect the amounts actually received by a smoker. Research that measured markers of nicotine and certain cancer-causing chemicals in smokers found that they took in the same amounts whatever the tar rating of the cigarettes they smoked. Smokers change the way they smoke – such as taking bigger or more frequent puffs, blocking filter holes or smoking more cigarettes in total – in order to satisfy their nicotine cravings.In 2003 EU legislation came into force banning tobacco companies from using phrases like ‘light’, ‘mild’ or ‘low-tar’ to describe their products because these could mislead people into believing such products were safer or healthier.

Alcohol worsens the effect of smoking

Alcohol has also been shown to be a cause of mouth, oesophageal and liver cancers, among others11. And scientists have found that together, the effects of alcohol and tobacco are worse than for either one of them by itself.

Passive smoking causes cancer and other diseases

There is clear evidence that breathing in other people’s smoke causes cancer in non-smokers. Second-hand smoke, also known as environmental tobacco smoke or passive smoking, exposes people to cancer-causing chemicals.People who have never smoked have their risk of lung cancer increased by around a quarter if they have colleagues who smoke at work or have a spouse who smokes. The risk increases the more second-hand smoke they’re exposed to, workers exposed to the highest levels can have their risk of lung cancer doubled.Second-hand smoke can reach high levels in enclosed spaces such as within the home or inside a car. Studies have shown that even when you open the windows levels can be dangerously high.Second-hand smoke also causes other health problems in non-smokers including heart disease and respiratory diseases including asthma in children. And it may increase the risk of pharyngeal and laryngeal cancers. 

Tobacco in pipes, cigars, bidis and shisha can also cause cancer

It’s not just cigarettes which increase the risk of cancer – other ways of smoking tobacco including pipes, cigars, bidis and shisha are also linked with the disease. Reviews of the evidence by the International Agency for Research on Cancer have concluded that smoking cigars, pipes or bidis increases the risk of lung, mouth, throat, voice box, gullet (oesophagus) and stomach cancers. And cigar smoking has also been linked with pancreatic cancer. Shisha smoking has been less well studied but the evidence suggests it is linked to lung cancer and possibly other cancers .Because they think it is healthier, some cigarette smokers switch to smoking a cigar or pipe. But aside from the health risks associated with pipes and cigars, research has also shown that because these people are more likely to inhale the smoke than people who have only ever smoked a cigar or pipe, the switch makes little difference to their chance of dying as a result of smoking.

Smokeless tobacco can also cause cancer

There are a wide variety of smokeless tobacco products used around the world. In the UK chewing tobacco, which may be used as part of betel quid, paan or zarda, is popular with South Asian communities. Tobacco can also be chewed or sucked by itself, or taken as snuff.Smokeless tobacco has been shown to cause mouth, gullet (oesophageal) and pancreatic cancers. Chewing betel quid with tobacco has also been shown to cause cancer of the mouth, upper throat and gullet (oesophagus). The size of the cancer risks associated with using smokeless tobacco are likely to vary depending on the type of product and the way it’s used .It has been suggested that smokeless tobacco could be used to help people stop using smoking tobacco, and that falling smoking rates in Sweden have been linked to people switching to a type of smokeless tobacco called ‘snus’. But a review of the evidence by the IARC in 2007 concluded that the available evidence does not support these claims 66.There are many cancer-causing chemicals present in smokeless tobacco, including in ‘snus’ ,. Studies have shown that these harmful chemicals, such as tobacco-specific nitrosamines (TSNAs), are taken up by people using these products .

Smokeless tobacco also contains nicotine, and is therefore addictive E-cigarettes have not yet been proven to support smoking cessation

Although some users have claimed that e-cigarettes have helped them stop smoking, there is not enough scientific evidence to show whether they are effective, and as safe as current licensed cessation aids (such as nicotine patches) . So far there has only been one trial comparing the use of e-cigarettes to another stop smoking aid (patches in this case) . Unfortunately this trial was too small to show a significant difference between the likelihood of quitting .However e-cigarettes are almost certainly far safer than smoking tobacco. E-cigarettes may play a role in helping smokers quit but larger trials are needed as scientific evidence that they really work, to explore how best to use them and to see how they  compare to other methods of quitting .

Diet and Physical Activity

Diet and Physical Activity: What’s the Cancer Connection?

How much do daily habits like diet and exercise affect your risk for cancer? Much more than you might think. Research has shown that poor diet and not being active are 2 key factors that can increase a person’s cancer risk. The good news is that you do something about this.

Besides quitting smoking, some of the most important things you can do to help reduce your cancer risk are:

• Get to and stay at a healthy weight throughout life.

Be physically active on a regular basis.

Make healthy food choices with a focus on plant-based foods.

The evidence for this is strong: Each year, about 589,430 Americans die of cancer; around one-third of these deaths are linked to poor diet, physical inactivity, and carrying too much weight.

• Control your weight.

Getting to and staying at a healthy weight is important to reduce the risk of cancer and other chronic diseases, such as heart disease and diabetes. Being overweight or obese increases the risk of several cancers, including those of the breast (in women past menopause), colon and rectum, endometrium (the lining of the uterus), esophagus, pancreas, and kidney, among others.

Being overweight can increase cancer risk in many ways. One of the main ways is that excess weight causes the body to produce and circulate more estrogen and insulin, hormones that can stimulate cancer growth.

• What’s a healthy weight?

One of the best ways to get an idea if you are at a healthy weight is to check your Body Mass Index (BMI), a score based on the relationship between your height and weight. Use our easy online BMI calculator to find out your score.

To reduce cancer risk, most people need to keep their BMIs below 25. Ask your doctor what your BMI number means and what action (if any) you should take.

If you are trying to control your weight, a good first step is to watch portion sizes, especially of foods high in calories, fat, and added sugars. Also try to limit your intake of high-calorie foods and drinks. Try writing down what and how much you eat and drink for a week, then see where you can cut down on portion sizes, cut back on some not-so-healthy foods and drinks, or both!

For those who are overweight or obese, losing even a small amount of weight has health benefits and is a good place to start.

• Be more active.

Watching how much you eat will help you control your weight. The other key is to be more physically active. Being active helps reduce your cancer risk by helping with weight control. It can also help improve your hormone levels and the way your immune system works.

More good news – physical activity helps you reduce your risk of heart disease and diabetes, too! So grab your athletic shoes and head out the door!

The latest recommendations for adults call for at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity activity each week, or an equivalent combination, preferably spread throughout the week. This is over and above usual daily activities like using the stairs instead of the elevator at your office or doing housework. For kids, the recommendation is at least 60 minutes of moderate or vigorous intensity activity each day, with vigorous intensity activity occurring at least 3 days each week.

Moderate activities are those that make you breathe as hard as you would during a brisk walk. This includes things like walking, biking, even housework and gardening. Vigorous activities make you use large muscle groups and make your heart beat faster, make you breathe faster and deeper, and also make you sweat.

It’s also important to limit sedentary behavior such as sitting, lying down, watching television, or other forms of screen-based entertainment.

Being more physically active than usual, no matter what your level of activity, can have many health benefits.

• Eat healthy foods.

Eating well is an important part of improving your health and reducing your cancer risk. Take a good hard look at what you typically eat each day and try these tips to build a healthy diet plan for yourself and your family:

• Choose foods and drinks in amounts that help you get to and maintain a healthy weight.

Read food labels to become more aware of portion sizes and calories. Be aware that “low-fat” or “non-fat” does not necessarily mean “low-calorie.”

Eat smaller portions when eating high-calorie foods.

Choose vegetables, whole fruit, legumes such as peas and beans, and other low-calorie foods instead of calorie-dense foods such as French fries, potato and other chips, ice cream, donuts, and other sweets.

Limit your intake of sugar-sweetened beverages such as soft drinks, sports drinks, and fruit-flavored drinks.

When you eat away from home, be especially mindful to choose food low in calories, fat, and added sugar, and avoid eating large portion sizes.

Limit how much processed meat and red meat you eat.

Limit your intake of processed meats such as bacon, sausage, lunch meats, and hot dogs.

Choose fish, poultry, or beans instead of red meat (beef, pork, and lamb).

If you eat red meat, choose lean cuts and eat smaller portions.

Prepare meat, poultry, and fish by baking, broiling, or poaching rather than by frying or charbroiling.

Eat at least 2½ cups of vegetables and fruits each day.

Include vegetables and fruits at every meal and snack.

Eat a variety of vegetables and fruits each day.

Emphasize whole fruits and vegetables; choose 100% juice if you drink vegetable or fruit juices.

Limit your use of creamy sauces, dressings, and dips with fruits and vegetables.

Choose whole grains instead of refined grain products.

Choose whole-grain breads, pasta, and cereals (such as barley and oats) instead of breads, cereals, and pasta made from refined grains, and brown rice instead of white rice.

Limit your intake of refined carbohydrate foods, including pastries, candy, sugar-sweetened breakfast cereals, and other high-sugar foods.

If you drink alcohol, limit how much

People who drink alcohol should limit their intake to no more than 2 drinks per day for men and 1 drink per day for women. The recommended limit is lower for women because of their smaller body size and slower breakdown of alcohol.

A drink of alcohol is defined as 12 ounces of beer, 5 ounces of wine, or 1½ ounces of 80-proof distilled spirits (hard liquor). In terms of cancer risk, it is the amount of alcohol, not the type of alcoholic drink that is important.

These daily limits do not mean it’s safe to drink larger amounts on fewer days of the week, since this can lead to health, social, and other problems.

• Reducing cancer risk in our communities

Adopting a healthier lifestyle is easier for people who live, work, play, or go to school in an environment that supports healthy behaviors. Working together, communities can create the type of environment where healthy choices are easy to make.

We all can be part of these changes: Let’s ask for healthier food choices at our workplaces and schools. For every junk food item in the vending machine, ask for a healthy option, too. Support restaurants that help you to eat well by offering options like smaller portions, lower-calorie items, and whole-grain products. And let’s help make our communities safer and more appealing places to walk, bike, and be active.

• The bottom line

It has been estimated that as much as one-third of all cancer deaths in the US are related to diet and activity factors. Let’s challenge ourselves to lose some extra pounds, increase our physical activity, make healthy food choices, limit alcohol, and look for ways to make our communities healthier places to live, work, and play.

Sun and UV Exposure

• Cosmetic Procedures: Sun Exposure and Skin Cancer

The sun's rays make us feel good, and in the short term, make us look good. But our love affair isn't a two-way street. Exposure to sun causes most of the wrinkles and age spots on our faces. Consider this: One woman at age 40 who has protected her skin from the sun actually has the skin of a 30-year-old!
We often associate a glowing complexion with good health, but skin color obtained from being in the sun – or in a tanning booth – actually accelerates the effects of aging and increases your risk for developing skin cancer.
Sun exposure causes most of the skin changes that we think of as a normal part of aging. Over time, the sun's ultraviolet (UV) light damages the fibers in the skin called elastin. When these fibers break down, the skin begins to sag, stretch, and lose its ability to go back into place after stretching. The skin also bruises and tears more easily -- taking longer to heal. So while sun damage to the skin may not be apparent when you're young, it will definitely show later in life.

• How Does the Sun Change My Skin?

Exposure to the sun causes:
Pre-cancerous (actinic keratosis) and cancerous (basal cell carcinoma, squamous cell carcinoma and melanoma) skin lesions - due to decreases in the skin's immune function
Benign tumors
Fine and coarse wrinkles
Freckles
Discolored areas of the skin, called mottled pigmentation
Sallowness -- a yellow discoloration of the skin
Telangiectasias -- the dilation of small blood vessels under the skin
Elastosis -- the destruction of the elastic and collagen tissue (causing lines, wrinkles and sagging skin)

• What Causes Skin Cancer?

Skin cancer is the most prevalent form of all cancers in the U.S. and the number of cases continues to rise. It is the uncontrolled growth of abnormal skin cells. This rapid growth results in tumors, which are either benign (noncancerous) or malignant (cancerous).
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and melanoma. Basal cell and squamous cell cancers are less serious types and make up 95% of all skin cancers. Also referred to as non-melanoma skin cancers, they are highly curable when treated early. Melanoma, made up of abnormal skin pigment cells called melanocytes, is the most serious form of skin cancer and causes 75% of all skin cancer deaths. Left untreated, it can spread to other organs and is difficult to control.

• What Causes Skin Cancer? continued...

Ultraviolet (UV) radiation from the sun is the number-one cause of skin cancer, but UV light from tanning beds is just as harmful. Exposure to sunlight during the winter months puts you at the same risk as exposure during the summertime because UVA rays are present in daylight.
Cumulative sun exposure causes mainly basal cell and squamous cell skin cancer, while episodes of severe sunburns, usually before age 18, can contribute to developing melanoma. Other less common causes are repeated X-ray exposure and occupational exposure to certain chemicals.

• Who Is at Risk for Skin Cancer?

Although anyone can get skin cancer, the risk is greatest for people who have fair or freckled skin that burns easily, light eyes and blond or red hair. Darker skinned individuals are also susceptible to all types of skin cancer, although their risk is substantially lower.
Aside from complexion, other risk factors include having a family history or personal history of skin cancer, having an outdoor job and living in a sunny climate. A history of severe sunburns and an abundance (greater than 30) of large and irregularly-shaped moles are risk factors unique to melanoma.

• What Are the Symptoms of Skin Cancer?

The most common warning sign of skin cancer is a change on the skin, typically a new mole or skin lesion or a change in an existing mole.
Basal cell carcinoma may appear as a small, smooth, pearly or waxy bump on the face, ears or neck, or as a flat pink, red or brown lesion on the trunk or arms and legs.
SquamouWhen looking for melanoma, think of the ABCDE rule that tells you the signs to watch for:s cell carcinoma can appear as a firm, red nodule, or as a rough, scaly flat lesion that may bleed and become crusty. Both basal cell and squamous cell cancers mainly occur on areas of the skin frequently exposed to the sun, but can occur anywhere.
Melanoma usually appears as a pigmented patch or bump but can also be red or white. It may resemble a normal mole, but usually has a more irregular appearance.
Asymmetry - the shape of one half doesn't match the other
Border - edges are ragged or blurred
Color - uneven shades of brown, black, tan, red, white or blue
Diameter - A significant change in size (greater than 6mm)- although any mole that begins enlarging should be brought to the attention of your dermatologist. Many melanomas are being diagnosed at much smaller diameters.
Evolving - any new spot of mole changing in color, shape or size
How is Skin Cancer Diagnosed?
Skin cancer is usually diagnosed by performing a biopsy. This involves taking a sample of the tissue, which is then placed under a microscope and examined by a dermatopathologist, or doctor who specializes in examining skin tissue.

• How is Skin Cancer Treated?

Treatment of skin cancer is individualized and is determined by the type of skin cancer, its size and location, and the patient's preference.
Standard treatments for non-melanoma skin cancer (basal cell or squamous cell carcinomas) include:
Primary Excision - excision of the skin cancer under local anesthesia with a margin of normal tissue.
Mohs surgery (for high-risk skin cancers or skin cancers in high risk areas) – excision of cancer with immediate microscopic examination to ensure clear margins- important to spare tissue and ensure complete removal of the cancer.
Electrodesiccation and curettage – physically scraping away the skin cancer cells followed by electrosurgery
Cryosurgery or freezing
Topical chemotherapeutic creams
Standard treatments for melanoma skin cancer include:
Wide surgical excision
Sentinel lymph node mapping (for deeper lesions) to determine if the melanoma has spread to local lymph nodes
Drugs (chemotherapy, biological response modifiers) for widespread metastatic disease
Radiation therapy for local control of advanced melanoma in areas such as the brain
New methods in clinical trials

• How Can I Help Prevent Skin Cancer?

Nothing can completely undo sun damage, although the skin can somewhat repair itself, especially with on-going sun protection. So, it's never too late to begin protecting yourself from the sun. Your skin does change with age -- for example, you sweat less and your skin can take longer to heal, but you can delay these changes by staying out of the sun. Follow these tips to help prevent skin cancer:
Apply sunscreen with a sun protection factor (SPF) of 30 or greater (for UVB protection) and zinc oxide (for UVA protection) 20 minutes before sun exposure and every 2 hours thereafter, more if you are sweating or swimming.
Select clothing, cosmetic products, and contact lenses that offer UV protection.
Wear sunglasses with total UV protection and a wide-brimmed hat to shade your face and neck.
Avoid direct sun exposure as much as possible during peak UV radiation hours (between 10:00 a.m. and 2:00 p.m.).
Perform skin self-exams regularly (at least monthly) to become familiar with existing growths and to notice any changes or new growths.
Eighty percent of a person's lifetime sun exposure is acquired before age 18. As a parent, be a good role model and foster skin cancer prevention habits in your child.

Radiation Exposure and Cancer Risk

• Mechanism

Cancer is a stochastic effect of radiation, meaning that the probability of occurrence increases with effective radiation dose, but the severity of the cancer is independent of dose. The speed at which cancer advances, the prognosis, the degree of pain, and every other feature of the disease are not functions of the radiation dose to which the person is exposed. This contrasts with the deterministic effects of acute radiation syndrome which increase in severity with dose above a threshold. Cancer starts with a single cell whose operation is disrupted. Normal cell operation is controlled by the chemical structure of DNA molecules, also called chromosomes.

When radiation deposits enough energy in organic tissue to cause ionization, this tends to break molecular bonds, and thus alter the molecular structure of the irradiated molecules. Less energetic radiation, such as visible light, only causes excitation, not ionization, which is usually dissipated as heat with relatively little chemical damage. Ultraviolet light is usually categorized as non-ionizing, but it is actually in an intermediate range that produces some ionization and chemical damage. Hence the carcinogenic mechanism of ultraviolet radiation is similar to that of ionizing radiation.

Unlike chemical or physical triggers for cancer, penetrating radiation hits molecules within cells randomly.[note 1] Molecules broken by radiation can become highly reactive free radicals that cause further chemical damage. Some of this direct and indirect damage will eventually impact chromosomes and epigenetic factors that control the expression of genes. Cellular mechanisms will repair some of this damage, but some repairs will be incorrect and some chromosome abnormalities will turn out to be irreversible.

DNA double-strand breaks (DSBs) are generally accepted to be the most biologically significant lesion by which ionizing radiation causes cancer. In vitro experiments show that ionizing radiation cause DSBs at a rate of 35 DSBs per cell per Gray, and removes a portion of the epigenetic markers of the DNA, which regulate the gene expression. Most of the induced DSBs are repaired within 24h after exposure, however, 25% of the repaired strands are repaired incorrectly and about 20% of fibroblast cells that were exposed to 200mGy died within 4 days after exposure. A portion of the population possess a flawed DNA repair mechanism, and thus suffer a greater insult due to exposure to radiation.

Major damage normally results in the cell dying or being unable to reproduce. This effect is responsible for acute radiation syndrome, but these heavily damaged cells cannot become cancerous. Lighter damage may leave a stable, partly functional cell that may be capable of proliferating and eventually developing into cancer, especially if tumor suppressor genes are damaged. The latest research suggests that mutagenic events do not occur immediately after irradiation. Instead, surviving cells appear to have acquired a genomic instability which causes an increased rate of mutations in future generations. The cell will then progress through multiple stages of neoplastic transformation that may culminate into a tumor after years of incubation. The neoplastic transformation can be divided into three major independent stages: morphological changes to the cell, acquisition of cellular immortality (losing normal, life-limiting cell regulatory processes), and adaptations that favor formation of a tumor.

In some cases, a small radiation dose reduces the impact of a subsequent, larger radiation dose. This has been termed an 'adaptive response' and is related to hypothetical mechanisms of hormesis.

A latent period of decades may elapse between radiation exposure and the detection of cancer. Those cancers that may develop as a result of radiation exposure are indistinguishable from those that occur naturally or as a result of exposure to other carcinogens. Furthermore, National Cancer Institute literature indicates that chemical and physical hazards and lifestyle factors, such as smoking, alcohol consumption, and diet, significantly contribute to many of these same diseases. Evidence from uranium miners suggests that smoking may have a multiplicative, rather than additive, interaction with radiation. Evaluations of radiation's contribution to cancer incidence can only be done through large epidemiological studies with thorough data about all other confounding risk factors.

• Skin cancer

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.

Skin cancer may occur following ionizing radiation exposure following a latent period averaging 20 to 40 years.A Chronic radiation keratosis is a precancerous keratotic skin lesion that may arise on the skin many years after exposure to ionizing radiation. Various malignancies may develop, most frequency basal-cell carcinoma followed by squamous-cell carcinoma.Elevated risk is confined to the site of radiation exposure.Several studies have also suggested the possibility of a causal relationship between melanoma and ionizing radiation exposure. The degree of carcinogenic risk arising from low levels of exposure is more contentious, but the available evidence points to an increased risk that is approximately proportional to the dose received. Radiologists and radiographers are among the earliest occupational groups exposed to radiation. It was the observation of the earliest radiologists that led to the recognition of radiation-induced skin cancer—the first solid cancer linked to radiation—in 1902. While the incidence of skin cancer secondary to medical ionizing radiation was higher in the past, there is also some evidence that risks of certain cancers, notably skin cancer, may be increased among more recent medical radiation workers, and this may be related to specific or changing radiologic practices. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation.

• Epidemiology

Cancer is a stochastic effect of radiation, meaning that it only has a probability of occurrence, as opposed to deterministic effects which always happen over a certain dose threshold. The consensus of the nuclear industry, nuclear regulators, and governments, is that the incidence of cancers due to ionizing radiation can be modeled as increasing linearly with effective radiation dose at a rate of 5.5% per sievert. Individual studies, alternate models, and earlier versions of the industry consensus have produced other risk estimates scattered around this consensus model. There is general agreement that the risk is much higher for infants and fetuses than adults, higher for the middle-aged than for seniors, and higher for women than for men, though there is no quantitative consensus about this. This model is widely accepted for external radiation, but its application to internal contamination is disputed. For example, the model fails to account for the low rates of cancer in early workers at Los Alamos National Laboratory who were exposed to plutonium dust, and the high rates of thyroid cancer in children following the Chernobyl accident, both of which were internal exposure events. The European Committee on Radiation Risk calls the ICRP model "fatally flawed" when it comes to internal exposure.

Radiation can cause cancer in most parts of the body, in all animals, and at any age, although radiation-induced solid tumors usually take 10–15 years, and can take up to 40 years, to become clinically manifest, and radiation-induced leukemias typically require 2–10 years to appear. Some people, such as those with nevoid basal cell carcinoma syndrome or retinoblastoma, are more susceptible than average to developing cancer from radiation exposure. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

Radiation exposure can cause cancer in any living tissue, but high-dose whole-body external exposure is most closely associated with leukemia, reflecting the high radiosensitivity of bone marrow. Internal exposures tend to cause cancer in the organs where the radioactive material concentrates, so that radon predominantly causes lung cancer, iodine-131 is most likely to cause thyroid cancer, etc.

• Data sources

Increased Risk of Solid Cancer with Dose for A-bomb survivors

The associations between ionizing radiation exposure and the development of cancer are based primarily on the "LSS cohort" of Japanese atomic bomb survivors, the largest human population ever exposed to high levels of ionizing radiation. Additional data has been collected from recipients of selected medical procedures and the 1986 Chernobyl disaster. There is a clear link (see the UNSCEAR 2000 Report, Volume 2: Effects) between the Chernobyl accident and the unusually large number, approximately 1,800, of thyroid cancers reported in contaminated areas, mostly in children.

For low levels of radiation, the biological effects are so small they may not be detected in epidemiological studies. Although radiation may cause cancer at high doses and high dose rates, public health data regarding lower levels of exposure, below about 10 mSv (1,000 mrem), are harder to interpret. To assess the health impacts of lower radiation doses, researchers rely on models of the process by which radiation causes cancer; several models that predict differing levels of risk have emerged.

Studies of occupational workers exposed to chronic low levels of radiation, above normal background, have provided mixed evidence regarding cancer and transgenerational effects. Cancer results, although uncertain, are consistent with estimates of risk based on atomic bomb survivors and suggest that these workers do face a small increase in the probability of developing leukemia and other cancers. One of the most recent and extensive studies of workers was published by Cardis, et al. in 2005 .There is evidence that low level, brief radiation exposures are not harmful.

Modelling

Alternative assumptions for the extrapolation of the cancer risk vs. radiation dose to low-dose levels, given a known risk at a high dose: supra-linearity (A), linear (B), linear-quadratic (C) and hormesis (D).

The linear dose-response model suggests that any increase in dose, no matter how small, results in an incremental increase in risk. The linear no-threshold model (LNT) hypothesis is accepted by the International Commission on Radiological Protection (ICRP) and regulators around the world. According to this model, about 1% of the global population develop cancer as a result of natural background radiation at some point in their lifetime. For comparison, 13% of deaths in 2008 are attributed to cancer, so background radiation could plausibly be a small contributor.

Many parties have criticized the ICRP's adoption of the linear no-threshold model for exaggerating the effects of low radiation doses. The most frequently cited alternatives are the “linear quadratic” model and the “hormesis” model. The linear quadratic model is widely viewed in radiotherapy as the best model of cellular survival, and it is the best fit to leukemia data from the LSS cohort.

Linear no-threshold F(D)=α⋅D

Linear quadratic F(D)=α⋅D+β⋅D2

Hormesis F(D)=α⋅[D−β]

In all three cases, the values of alpha and beta must be determined by regression from human exposure data. Laboratory experiments on animals and tissue samples is of limited value. Most of the high quality human data available is from high dose individuals, above 0.1 Sv, so any use of the models at low doses is an extrapolation that might be under-conservative or over-conservative. There is not enough human data available to settle decisively which of these model might be most accurate at low doses. The consensus has been to assume linear no-threshold because it the simplest and most conservative of the three.

Radiation hormesis is the conjecture that a low level of ionizing radiation (i.e., near the level of Earth's natural background radiation) helps "immunize" cells against DNA damage from other causes (such as free radicals or larger doses of ionizing radiation), and decreases the risk of cancer. The theory proposes that such low levels activate the body's DNA repair mechanisms, causing higher levels of cellular DNA-repair proteins to be present in the body, improving the body's ability to repair DNA damage. This assertion is very difficult to prove in humans (using, for example, statistical cancer studies) because the effects of very low ionizing radiation levels are too small to be statistically measured amid the "noise" of normal cancer rates.

The idea of radiation hormesis is considered unproven by regulatory bodies. If the hormesis model turns out to be accurate, it is conceivable that current regulations based on the LNT model will prevent or limit the hormetic effect, and thus have a negative impact on health.

Other non-linear effects have been observed, particularly for internal doses. For example, iodine-131 is notable in that high doses of the isotope are sometimes less dangerous than low doses, since they tend to kill thyroid tissues that would otherwise become cancerous as a result of the radiation. Most studies of very-high-dose I-131 for treatment of Graves disease have failed to find any increase in thyroid cancer, even though there is linear increase in thyroid cancer risk with I-131 absorption at moderate doses.

• Causes

According to the prevalent model, any radiation exposure can increase the risk of cancer. Typical contributors to such risk include natural background radiation, medical procedures, occupational exposures, nuclear accidents, and many others. Some major contributors are discussed below.

Background

Radon is responsible for the worldwide majority of the mean public exposure to ionizing radiation. It is often the single largest contributor to an individual's background radiation dose, and is the most variable from location to location. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as attics, and basements. It can also be found in some spring waters and hot springs.

Epidemiological evidence shows a clear link between lung cancer and high concentrations of radon, with 21,000 radon-induced U.S. lung cancer deaths per year—second only to cigarette smoking—according to the United States Environmental Protection Agency.Thus in geographic areas where radon is present in heightened concentrations, radon is considered a significant indoor air contaminant.

Residential exposure to radon gas has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.

Medical

In industrialized countries, Medical imaging contributes almost as much radiation dose to the public as natural background radiation. Collective dose to Americans from medical imaging grew by a factor of six from 1990 to 2006, mostly due to growing use of 3D scans that impart much more dose per procedure than traditional radiographs.CT scans alone, which account for half the medical imaging dose to the public, are estimated to be responsible for 0.4% of current cancers in the United States, and this may increase to as high as 1.5-2% with 2007 rates of CT usage; however, this estimate is disputed. Other nuclear medicine techniques involve the injection of radioactive pharmaceuticals directly into the bloodstream, and radiotherapy treatments deliberately deliver lethal doses (on a cellular level) to tumors and surrounding tissues.

It has been estimated that CT scans performed in the US in 2007 alone will result in 29,000 new cancer cases in future years. This estimate is criticized by the American College of Radiology (ACR), which maintains that the life expectancy of CT scanned patients is not that of the general population and that the model of calculating cancer is based on total-body radiation exposure and thus faulty.

Occupational

In accordance with ICRP recommendations, most regulators permit nuclear energy workers to receive up to 20 times more radiation dose than is permitted for the general public. Higher doses are usually permitted when responding to an emergency. The majority of workers are routinely kept well within regulatory limits, while a few essential technicians will routinely approach their maximum each year. Accidental overexposures beyond regulatory limits happen globally several times a year.Astronauts on long missions are at higher risk of cancer, see cancer and spaceflight.

Some occupations are exposed to radiation without being classed as nuclear energy workers. Airline crews receive occupational exposures from cosmic radiation because of reduced atmospheric shielding at altitude. Mine workers receive occupational exposures to radon, especially in uranium mines. Anyone working in a granite building, such as the US Capitol, is likely to receive a dose from natural uranium in the granite.

Accidental

Chernobyl radiation map from 1996

Nuclear accidents can have dramatic consequences to their surroundings, but their global impact on cancer is less than that of natural and medical exposures.

The most severe nuclear accident is probably the Chernobyl disaster. In addition to conventional fatalities and acute radiation syndrome fatalities, nine children died of thyroid cancer), and it is estimated that there may be up to 4,000 excess cancer deaths among the approximately 600,000 most highly exposed people. Of the 100 million curies (4 exabecquerels) of radioactive material, the short lived radioactive isotopes such as Chernobyl released were initially the most dangerous. Due to their short half-lives of 5 and 8 days they have now decayed, leaving the more long-lived 137Cs (with a half-life of 30.07 years) and 90Sr (with a half-life of 28.78 years) as main dangers.

In March 2011, an earthquake and tsunami caused damage that led to explosions and partial meltdowns at the Fukushima I Nuclear Power Plant in Japan. Significant release of radioactive material took place following hydrogen explosions at three reactors, as technicians tried to pump in seawater to keep the uranium fuel rods cool, and bled radioactive gas from the reactors in order to make room for the seawater. Concerns about the large-scale release of radioactivity resulted in 20 km exclusion zone being set up around the power plant and people within the 20–30 km zone being advised to stay indoors. On March 24, 2011, Japanese officials announced that "radioactive iodine-131 exceeding safety limits for infants had been detected at 18 water-purification plants in Tokyo and five other prefectures".

Other serious radiation accidents include the Kyshtym disaster (estimated 49 to 55 cancer deaths), and the Windscale fire (an estimated 33 cancer deaths).

The Transit 5BN-3 SNAP 9A accident. On April 21, 1964, the satellite containing plutonium burnt up in the atmosphere. Dr. John Gofman claimed it increased the rate of lung cancer worldwide. He said "Although it is impossible to estimate the number of lung cancers induced by the accident, there is no question that the dispersal of so much Plutonium238 would add to the number of lung cancer diagnosed over many subsequent decades."

Public safety

Low-dose exposures, such as living near a nuclear power plant, are generally believed to have no or very little effect on cancer development, barring accidents.Greater concerns include radon in buildings and overuse of medical imaging.

The International Commission on Radiological Protection (ICRP) recommends limiting artificial irradiation of the public to an average of 1 mSv (0.001 Sv) of effective dose per year, not including medical and occupational exposures.[3] For comparison, radiation levels inside the US capitol building are 0.85 mSv/yr, close to the regulatory limit, because of the uranium content of the granite structure.According to the ICRP model, someone who spent 20 years inside the capitol building would have an extra one in a thousand chance of getting cancer, over and above any other existing risk. (20 yr X 0.85 mSv/yr X 0.001 Sv/mSv X 5.5%/Sv = ~0.1%) That "existing risk" is much higher; an average American would have a one in ten chance of getting cancer during this same 20-year period, even without any exposure to artificial radiation.

Internal contamination due to ingestion, inhalation, injection, or absorption is a particular concern because the radioactive material may stay in the body for an extended period of time, "committing" the subject to accumulating dose long after the initial exposure has ceased, albeit at low dose rates. Over a hundred people, including Eben Byers and the radium girls, have received committed doses in excess of 10 Gy and went on to die of cancer or natural causes, whereas the same amount of acute external dose would invariably cause an earlier death by acute radiation syndrome.

Internal exposure of the public is controlled by regulatory limits on the radioactive content of food and water. These limits are typically expressed in becquerel/kilogram, with different limits set for each contaminant.

History

Although radiation was discovered in late 19th century, the dangers of radioactivity and of radiation were not immediately recognized. Acute effects of radiation were first observed in the use of X-rays when Wilhelm Röntgen intentionally subjected his fingers to X-rays in 1895. He published his observations concerning the burns that developed, though he attributed them to ozone rather than to X-rays. His injuries healed later.

The genetic effects of radiation, including the effects on cancer risk, were recognized much later. In 1927 Hermann Joseph Muller published research showing genetic effects, and in 1946 was awarded the Nobel prize for his findings. Radiation was soon linked to bone cancer in the radium dial painters, but this was not confirmed until large-scale animal studies after world war II. The risk was then quantified through long-term studies of atomic bomb survivors.

Before the biological effects of radiation were known, many physicians and corporations had begun marketing radioactive substances as patent medicine and radioactive quackery. Examples were radium enema treatments, and radium-containing waters to be drunk as tonics. Marie Curie spoke out against this sort of treatment, warning that the effects of radiation on the human body were not well understood. Curie later died of acute radiation syndrome, not cancer. Eben Byers, a famous American socialite, died of multiple cancers in 1932 after consuming large quantities of radium over several years; his death drew public attention to dangers of radiation. By the 1930s, after a number of cases of bone necrosis and death in enthusiasts, radium-containing medical products had nearly vanished from the market.

In the United States, the experience of the so-called Radium Girls, where thousands of radium-dial painters contracted oral cancers, popularized the warnings of occupational health associated with radiation hazards. Robley D. Evans, at MIT, developed the first standard for permissible body burden of radium, a key step in the establishment of nuclear medicine as a field of study. With the development of nuclear reactors and nuclear weapons in the 1940s, heightened scientific attention was given to the study of all manner of radiation effects.

Other Carcinogens

Occupational carcinogens

Occupational carcinogens are agents that pose a risk of cancer in several specific work-locations:

Carcinogen	Associated cancer sites or types	Occupational uses or sources
Arsenic and its compounds	Lung Skin Hemangiosarcoma	Smelting byproduct Component of: Alloys Electrical and semiconductor devices Medications (e.g. melarsoprol) Herbicides Fungicides Animal dips Drinking water from contaminated aquifers.
Asbestos	Lungs Asbestosis Gastrointestinal tract Pleural Mesothelioma Peritoneal Mesothelioma	Not in widespread use, but found in: Constructions Roofing papers Floor tiles Fire-resistant textiles Friction linings (only outside Europe) Replacement friction linings for automobiles still may contain asbestos
Benzene	Leukemia Hodgkin lymphoma	Light fuel oil Former use as solvent and fumigant Printing Lithography Paint Rubber Dry cleaning Adhesives Coatings Detergents
Beryllium and its compounds	Lung	Missile fuel Lightweight alloys Aerospace applications Nuclear reactors
Cadmium and its compounds[20]	Prostate	Yellow pigments Phosphors Solders Batteries Metal paintings and coatings
Hexavalent chromium(VI) compounds	Lung	Paints Pigments Preservatives
IC engine exhaust gas	Lung[21] Bladder[21]	Exhaust gas from engines
Ethylene oxide	Leukemia	Ripening agent for fruits and nuts Rocket propellant Fumigant for foodstuffs and textiles Sterilant for hospital equipment
Nickel	Nose Lung	Nickel plating Ferrous alloys Ceramics Batteries Stainless-steel welding byproduct
Radon and its decay products	Lung	Uranium decay Quarries and mines Cellars and poorly ventilated places
Vinyl chloride	Hemangiosarcoma Liver	Refrigerant Production of polyvinyl chloride Adhesive for plastics Former use in pressurized containers
Shift work that involves circadian disruption	Breast
Involuntary smoking (Passive smoking)	Lung
Radium-226, Radium-224, Plutonium-238, Plutonium-239 and other alpha particle emitters with high atomic weight	Bone (they are bone seekers) Liver	Nuclear fuel processing Radium dial manufacturing

Others

• Gasoline (contains aromatics)
• Lead and its compounds
• Alkylating antineoplastic agents (e.g. mechlorethamine)
• Other alkylating agents (e.g. dimethyl sulfate)
• Ultraviolet radiation from the sun and UV lamps
• Alcohol (causing head and neck cancers)
• Other ionizing radiation (X-rays, gamma rays, etc.)

Major carcinogens implicated in the four most common cancers worldwide

In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described. These four cancers are lung, breast, colon, and stomach cancers. Together they account for about 41% of worldwide cancer incidence and 42% of cancer deaths (for more detailed information on the carcinogens implicated in these and other cancers, see references).

Lung cancer

Lung cancer is the most common cancer in the world, both in terms of cases (1.6 million cases; 12.7% of total cancer cases) and deaths (1.4 million deaths; 18.2% of total cancer deaths). Lung cancer is largely caused by tobacco smoke. Risk estimates for lung cancer in the United States indicate that tobacco smoke is responsible for 90% of lung cancers. Other factors are implicated in lung cancer, and these factors can interact synergistically with smoking, so that total attributable risk adds up to more than 100%. These factors include occupational exposure to carcinogens (about 9-15%), radon (10%) and outdoor air pollution (1-2%). Tobacco smoke is a complex mixture of more than 5,300 identified chemicals. The most important carcinogens in tobacco smoke have been determined by a “Margin of Exposure” approach.Using this approach, the most important tumorigenic compounds in tobacco smoke were, in order of importance, acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, cadmium, acetaldehyde, ethylene oxide and isoprene. Most of these compounds cause DNA damage by forming DNA adducts or by inducing other alterations in DNA. DNA damages are subject to error-prone DNA repair or can cause replication errors. Such errors in repair or replication can result in mutations in tumor suppressor genes or oncogenes leading to cancer.

Breast cancer

Breast cancer is the second most common cancer [(1.4 million cases, 10.9%), but ranks 5th as cause of death (458,000, 6.1%)]. Increased risk of breast cancer is associated with persistently elevated blood levels of estrogen. Estrogen appears to contribute to breast carcinogenesis by three processes; (1) the metabolism of estrogen to genotoxic, mutagenic carcinogens, (2) the stimulation of tissue growth, and (3) the repression of phase II detoxification enzymes that metabolize ROS leading to increased oxidative DNA damage.The major estrogen in humans, estradiol, can be metabolized to quinone derivatives that form adducts with DNA. These derivatives can cause dupurination, the removal of bases from the phosphodiester backbone of DNA, followed by inaccurate repair or replication of the apurinic site leading to mutation and eventually cancer. This genotoxic mechanism may interact in synergy with estrogen receptor-mediated, persistent cell proliferation to ultimately cause breast cancer. Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk.

Colon cancer

Colorectal cancer is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)]. Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States. In addition, substantial evidence implicates bile acids as an important factor in colon cancer. Twelve studies (summarized in Bernstein et al.) indicate that the bile acids deoxycholic acid (DCA) and/or lithocholic acid (LCA) induce production of DNA damaging reactive oxygen species and/or reactive nitrogen species in human or animal colon cells. Furthermore 14 studies showed that DCA and LCA induce DNA damage in colon cells. Also 27 studies reported that bile acids cause programmed cell death (apoptosis). Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis. Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer. Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer. Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids. When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months.Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer.

Stomach cancer

Stomach cancer is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)]. Helicobacter pylori infection is the main causative factor in stomach cancer. Chronic gastritis (inflammation) caused by H. pylori is often long-standing if not treated. Infection of gastric epithelial cells with H. pylori results in increased production of reactive oxygen species (ROS). ROS cause oxidative DNA damage including the major base alteration 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG resulting from ROS is increased in chronic gastritis. The altered DNA base can cause errors during DNA replication that have mutagenic and carcinogenic potential. Thus H. pylori-induced ROS appear to be the major carcinogens in stomach cancer because they cause oxidative DNA damage leading to carcinogenic mutations.