Essay on Cancer Prevention | Types | Diseases | Biology

Read this essay to examine various agents that have the greatest impact in decreasing cancer incidence and deaths.

Not Smoking is the most Effective Way to Reduce the Risk of Developing a Fatal Cancer:

Cigarette smoking is the number one cause of preventable cancer deaths. Tobacco smoke contains dozens of carcinogenic chemicals. If people did not smoke ciga­rettes, roughly one of every three cancer deaths would be prevented.

Progress has been made over the past several decades in lowering smoking rates in the United States, but these gains have been offset by a growing epidemic of cigarette smoking elsewhere in the world. Even in the United States, close to 50 million people smoke cigarettes and smoking is the leading cause of preventable death, killing more people than AIDS, car accidents, murder, alcohol, illegal drugs, and suicides combined.

Figure 1 illustrates the trends in smoking rates in the United States since 1900. In the first half of the twentieth century, cigarette consumption increased from a yearly average of several dozen cigarettes per person in 1900 to more than 4000 per person in 1963. Then in 1964, the U.S. government published the first Surgeon General’s Report on Smoking and Health.

Based on an analysis of more than 7000 scien­tific investigations involving a variety of experimental and epidemiological approaches, the report concluded that cigarette smoking causes lung cancer. At that point, smoking rates in the United States stopped growing and slowly began to decline.

Improved education has played an important role in stimulating this decline. In general, smoking behavior is inversely related to a person’s overall level of education: Statistics show that roughly 30% of those without a high school diploma smoke cigarettes compared with about 10% of college graduates (Figure 2).

A variety of governmental actions have also contributed to the decline in smoking rates. Included in this category are laws requiring warning labels on cigarette packages, which inform people about the health hazards of tobacco, and high taxation of tobacco products and restrictions on smoking in public places, both of which tend to discourage smoking behaviors.

One obstacle to further progress is the difficulty that people encounter when they try to quit smoking. About half of all adult smokers express a desire to stop smoking and make at least one attempt to quit annually, yet fewer than 15% can refrain from smoking for more than 30 days.

The addictive power of the nicotine in tobacco is clearly a major impediment. Although some people overcome their nicotine addiction and quit smoking through sheer willpower, success rates are improved by supportive social arrangements, such as smoking cessation clinics, combined with drug treatments for nicotine dependence (e.g., nicotine patches or sprays and even antidepressants).

The motivation to quit might also be enhanced by better education regarding the dramatic drop in cancer risk that occurs after people stop smoking. In the 20-year period after quitting, lung cancer rates drop about tenfold to reach a level that is only slightly higher than that observed in individuals who have never smoked at all (Figure 3).

Moreover, the reduction in risk is not restricted to lung cancer. Smoking cessation is also associated with a decreased risk for cancers of the mouth, pharynx, larynx, esophagus, stomach, pancreas, uterine cervix, kidney, bladder, and colon, as well as leukemias.

Most tobacco-related cancers are linked to cigarette use, but other tobacco products—such as cigars, pipes, and smokeless tobacco—also cause cancer. Smoking cigars or a pipe triggers most of the same cancers as cigarettes, although the risk of lung cancer is less than with cigarettes because cigar or pipe smoke is not inhaled as deeply into the lungs.

Secondhand smoke can also cause cancer, although the risk is small compared with that associated with the direct use of tobacco products. Smoke is not even required for tobacco to exert its carcinogenic effects. Smokeless tobacco, which is chewed rather than smoked, causes numerous cancers of the mouth and throat, as well as some in the esophagus, stomach, and pancreas.

Alcohol Consumption is Associated with Cancer Risks, but also Cardiovascular Benefits when used in Moderate Amounts:

Alcohol consumption is associated with an increased risk for several types of cancer, including those of the mouth, pharynx, larynx, esophagus, stomach, and liver. Alcohol also interacts synergistically with tobacco to create cancer risks that are significantly greater than the sum of the effects produced by each acting alone. Limiting ones consumption of alcoholic beverages can therefore be an effective way of decreasing cancer risk.

Recommendations concerning alcohol consumption are complicated by the fact that unlike tobacco, which has no known health benefits, drinking moderate amounts of alcohol have been linked to about a 25% reduction in the risk of coronary heart disease.

The observation that the incidence of heart disease is relatively low in France despite high rates of saturated fat intake and smoking has led to the claim that red wine is particularly beneficial. However, epidemiological studies have failed to show a reliable difference in the heart benefits of drinking wine versus any other kind of alcohol.

Although alcohol’s beneficial effects on the heart have been fairly well established, these benefits are only seen at moderate levels of drinking—that is, no more than one to two drinks per day Alcohol consumption in excess of these levels has no discernable health benefits and creates a variety of health hazards, including an increased risk of cancer.

Anyone considering modest levels of alcohol con­sumption to exploit its beneficial effects on the heart might want to consider their own medical and family history to determine whether they have any predispositions to cardiovascular disease (where alcohol may be helpful) or cancer (where alcohol is more likely to be harmful).

Protecting against the Ultraviolet Radiation in Sunlight Reduces the Risk of Skin Cancer:

Skin cancer is the most frequent type of cancer worldwide but is among the easiest to prevent because its main cause—the ultraviolet radiation in sunlight—is well known and easy to protect against. Nonetheless, many people tend to be nonchalant about the dangers of sun­light and often fail to take adequate precautions to protect themselves, presumably because skin cancer is rarely fatal.

Such casual attitudes ignore the potential dangers of melanoma, a type of tumor whose tendency to metasta­size makes it the most lethal form of skin cancer. Melanomas represent only 5% of all skin cancers, but the 5% figure corresponds to enough cancer cases to place melanoma among the ten most common types of cancer.

Surveys have revealed that only one-third of Americans routinely take the three precautions that are most effective in preventing skin cancer:

(1) Restricting exposure to the sun, especially during midday when its ultraviolet radiation is the strongest;

(2) Wearing protective clothing; and

(3) Using sufficient amounts of sunscreen lotion.

Modern sunscreen lotions typically contain a mixture of ingredients for blocking and absorbing both UVB and UVA radiation. The strength of any given sunscreen is expressed by its SPF (sun-protection factor), a number that reflects how much time it takes for skin treated with sunscreen to burn compared with unprotected skin.

In other words, an SPF of 15 means that skin covered with sunscreen lotion will take 15 times longer to burn than unprotected skin. If it would normally take your skin 20 minutes to burn under a given set of sunlight conditions, proper use of a sunscreen lotion with an SPF of 15 would allow an exposure of 20 × 15 = 300 minutes (5 hours) before burning.

However, people typi­cally apply sunscreen in amounts that achieve only about half of the protection suggested by the SPF value. Thus in actual practice, a sunscreen labeled with an SPF of 30 needs to be used to achieve an SPF of 15.

It has been estimated that worldwide death rates from melanoma could be reduced by at least 50% if people restrict their exposure to intense sunlight, wear protective clothing, and properly use sunscreens that achieve an SPF of at least 15. In Australia, which has the highest incidence and death rates for skin cancer in the world, significant public education efforts have been made to try to influence sun-related attitudes and behaviors.

Three years after the launching of one prevention program in the Australian state of Victoria, the rate of sunburn dropped by 35% and people reported an increase in the wearing of hats and the use of sunscreen. Such results indicate that exposure to melanoma risk factors can be reduced fairly rapidly in response to health promotion campaigns.

Cancer Risks Created by Ionizing Radiation Tend to be Small for most Individuals:

Ionizing radiation is a high-energy type of radiation that removes electrons from molecules, thereby generating reactive ions that trigger DNA damage. Although large- dose exposures to ionizing radiation can cause many types of cancer, the doses encountered by the average person tend to be relatively small and account for less than 5% of all cancers.

Most of the ionizing radiation encountered on a regular basis—other than from the radioactive polonium in tobacco smoke—comes from natural background sources that cannot be readily avoided. The largest con­tributor to background radiation is radon, a radioactive gas emitted from underground rock formations in the earth’s crust.

Increased rates of lung cancer have been detected in underground mine workers exposed to high concentrations of radon for long periods of time, but comparable exposures are rarely experienced by the general public. Nevertheless, radon gas can seep into homes and accumulate in significant amounts if the venti­lation is inadequate, especially in regions of the country where large amounts of radon are emitted from the earth’s surface.

It is therefore advisable to test for radon levels in the home and, if they are exceptionally high, install an improved ventilation system in the basement to minimize the amount of radon that accumulates. Inexpensive radon testing kits suitable for this purpose are readily available at hardware stores or through public health agencies.

Natural background radiation accounts for about 80% of the ionizing radiation encountered by the average person. Of the remaining 20%, medical X-rays make the largest contribution. The health benefits of medical X-rays almost always outweigh the small risks involved, as long as X-rays are used only when a clear medical necessity exists.

A striking example of the dangers associated with unnec­essary medical X-rays occurred in the mid-1900s, when X-ray treatments were employed for clearing up facial acne in adolescent children. Individuals who received these treatments later developed thyroid cancer at signifi­cantly elevated rates.

Caution is also appropriate when using a high-dose X-ray procedure known as a computed tomography scan (CT scan) with young children. CT scans deliver up to 100 times more radiation than standard medical X-rays, and growing children are more sensitive than adults to the hazards of ionizing radiation.

In general, the average citizen tends to overestimate the risks posed by ionizing radiation. For comparison purposes, it is worth pointing out that among the Japanese residents of Hiroshima and Nagasaki who survived the immediate effects of the atomic explosions in 1945, only about 1% have died of radiation-induced cancers despite receiving radiation doses that were enormously greater than most people will encounter in their entire lifetimes.

Another interesting comparison involves perceptions regarding the dangers of the radiation associated with nuclear power. Living near a nuclear power plant normally exposes people to a radia­tion dose that is less than 1% of the background radiation we all receive from natural sources.

Yet when individuals are asked to rank their perceived risk of dying from various activities, nuclear power tends to be ranked ahead of much riskier activities, such as smoking cigarettes. In reality, the risk of dying from a radiation-induced cancer is quite small compared to most of the other risks associated with everyday life.

Avoiding Exposure to Certain Infectious Agents can Reduce Risks for Several Types of Cancer:

Although cancer is not usually perceived by the general public as being an infectious disease, roughly 15% of all cancers worldwide are linked to viral, bacterial, or para­sitic infections. People can therefore lower their risk of developing cancer by avoiding behaviors that expose them to the relevant infectious agents.

Human papillomavirus (HPV) is responsible for the largest number of virally linked cancers, mainly cervical cancer and, to a lesser extent, cancer of the penis. HPV is spread predominantly through sexual activity, so the risk of becoming infected can be reduced by avoiding sexual contact with multiple partners.

Using a condom also decreases the risk of HPV-induced cancers, but condoms are not fully protective because they fail to prevent the spread of HPV caused by contact with infected areas not covered by the condom.

The hepatitis B and hepatitis C viruses are responsible for most cases of liver cancer, a common form of cancer in Southeast Asia, China, and Africa. The hepatitis B virus is transmitted by exchange of bodily fluids, such as blood or semen, and can be easily spread through sexual activity. The proper use of latex condoms may help reduce the transmis­sion of hepatitis B, although the efficacy of the protection is unknown.

The hepatitis C virus is difficult to transmit by mechanisms other than direct contact with contaminated blood, so the main route for acquiring hepatitis C is through the sharing of dirty needles by intravenous drug users. Hepatitis viruses can also be transmitted by blood transfusions involving contaminated blood, but the blood supply used for medical purposes is now routinely screened for both the hepatitis B and hepatitis C viruses.

The only bacterium to be clearly linked to a human cancer is H. pylori, the main cause of stomach cancer. Roughly half the world’s population has been infected with H. pylori, and stomach cancer is therefore one of the top cancer killers globally.

Unlike the situation in many coun­tries, the prevalence of stomach cancer in the United States has declined substantially over the past several decades. One factor contributing to this marked decline is the widespread use of antibiotics, which has diminished the rate of H. pylori infections and thereby reduced the chances that people will come in contact with infected individuals.

Public health conditions also play an important role because transmission of H. pylori from person to person is facilitated by poor sanitation and crowded living environ­ments, which are less prevalent in the United States than in most developing countries (Figure 4).

Minimizing Exposure to Cancer-Causing Chemicals and Drugs can Reduce Cancer Risks:

More than two hundred chemical substances are known to cause—or are reasonably anticipated to cause—cancer in humans. These carcinogens are identified through the combined use of epidemiological evidence, animal testing, and the Ames test.

In practice, many of the chemicals that pose a signifi­cant cancer risk for humans were not identified until large numbers of cancers had arisen in workers exposed to these substances on a regular basis, especially in the rubber, chemical, plastic, mining, fuel, and dye industries. Although some of the responsible chemicals have now been banned from the workplace, others remain in use.

Workers must therefore take appropriate precautions, such as wearing masks and protective clothing, working in properly ventilated environments, and in some cases breathing through a respirator. As a result of the protec­tive measures that have been implemented, many of the occupational cancers that were once prevalent in the United States have declined in frequency, and workplace exposure to carcinogenic chemicals now accounts for less than 5% of all fatal cancers.

Chemical carcinogens are usually encountered in high concentration only in industrial workplaces or in tobacco smoke, but small amounts escape into the envi­ronment and contaminate the air we breathe, the water we drink, and the food we eat. It has therefore become fashionable to blame chemical pollution of the environ­ment for creating a cancer epidemic.

In fact, the data do not generally support this conclusion. Those chemical carcinogens that do pollute the environment tend to be present in concentrations that are thousands of times lower than typical workplace exposures, and most evi­dence suggests that the cancer threat they pose for the average person is quite small.

Of course, not everyone is an “average person”. For example, people who live near a site where toxic chemicals have been stored or released may be exposed to carcinogen concentrations that are thousands of times higher than those encountered by the general public.

Similarly, people who live in older buildings constructed with asbestos- containing materials may have higher-than-normal exposures to asbestos, especially if the construction mate­rials are deteriorating. Each person therefore needs to assess his or her own living situation to determine whether it involves any unusual contact with carcinogenic chemicals.

People also encounter high concentrations of specific chemicals when they take prescription drugs to treat chronic health problems. If a single drug is used for a protracted period of time, exposure to the substance in question will be high and it is important to know whether any cancer risks are involved.

There are number of pre­scription drugs that are already known to cause cancer. Because of the cancer hazard, most of these drugs are only prescribed for serious medical conditions in which the potential benefits of the drug in question far outweigh the risk that cancer might arise.

One problem in assessing the cancer hazards associ­ated with prescription drugs is that many years of human use may be required before the risks become apparent. For example, diethylstilbestrol (DES) is a synthetic estrogen that was prescribed to pregnant women for 30 years before its carcinogenic properties were discovered.

A more recent illustration is provided by hormone replacement therapy (HRT), a treatment sometimes prescribed for postmenopausal women because their lowered estrogen production can lead to several health problems, including increased risks for heart disease and osteoporosis (bone loss).

In the 1950s and 1960s, doctors routinely prescribed estrogen pills to postmenopausal women to prevent these problems. Then it was reported in the mid-1970s that estrogen administration creates an increased risk for uterine (endometrial) cancer, and its use began to decline.

When subsequent studies showed that the uterine cancer risk can be reduced or eliminated by combining estrogen with a progestin (a substance exhibiting progesterone-like activity), estrogen-progestin became the predominant form of HRT.

Although this newer type of HRT was initially thought to be safe, a study of 16,000 postmenopausal women sponsored by the Women’s Health Initiative was prematurely halted in 2002 when results began to suggest that the harmful effects associated with estrogen- progestin treatment outweigh the potential benefits.

One of the main problems to be reported was an increased incidence of breast cancer, but elevated rates for strokes, heart attacks, and blood clots were noticed as well. While the study also revealed that estrogen-progestin treatment lowers the risk of osteoporosis and colon cancer, these benefits were not considered to be sufficient to outweigh the other risks (Figure 5).

In 2003, a Swedish trial of HRT in postmenopausal women with a previous history of breast cancer was also halted, in this case because of an unacceptably high recurrence rate for breast cancer.

Reduced Consumption of Saturated Fat, Red Meat, Total Calories, and Dietary Carcinogens may Decrease Cancer Risk:

Of the thousands of chemicals we routinely encounter on a daily basis, most that enter our bodies are deliberately ingested because they are natural components of food. People who differ in the foods they eat also tend to differ in the cancers they develop, suggesting that diet has an important influence on cancer risks.

Unfortunately, the effects of individual foods are difficult to pinpoint because the eating habits of different people vary in numerous ways, making it hard to assess the impact of each ingredient.

The situation is further complicated by the fact that in any given diet, the carcinogenic effects of a substance found in one type of food may be blocked by the protective action of another substance present in the same diet.

In other words, cancer risk is related both to foods that increase cancer risk (whose intake should be reduced) and to foods that decrease cancer risk (whose intake should be increased).

It has been widely recommended that one component of the diet whose consumption should be reduced is animal fat. Unlike the fats found in fruits and vegetables, which are largely unsaturated, animal fats are rich in saturated fat. (The term saturated refers to a fat molecule in which all carbon atoms are bound to the maximum number of hydrogen atoms.)

Diets rich in saturated fat in general, and red meat in particular, have been linked in numerous epi­demiological studies to an elevated risk for several types of cancer, including colon, prostate, and breast cancers.

The main problem with this evidence is that most of the early epidemiological studies involved a retrospective approach in which people who had already developed cancer were asked to recall their dietary habits from many years earlier.

Because retrospective studies are susceptible to numerous sources of bias, several recent studies have used the more powerful prospective approach in which large groups of individuals without cancer are monitored into the future to see who develops the disease. Participants are repeatedly asked about their eating habits along the way, which provides more reliable information than can be obtained by asking people for their recollections many years later.

Large studies of this type have continued to support the conclusion that eating red meat is a risk factor for colon cancer, although the relationship between saturated fat intake and cancer risk is less certain. Part of the reason for this uncertainty may be that even large prospective studies are hampered by imprecise methods for assessing what people really eat.

The apparent linkage seen in some studies between saturated fat intake and cancer risk may arise in part because fats have higher calorie content than other nutrients. Two reasons exist for believing that extra calories are a cancer risk.

First, animal studies have shown that reducing the number of calories in the diet leads to a decrease in cancer rates, both for spontaneous tumors and for tumors induced by carcinogenic chemicals or radiation (Figure 6).

Second, people who eat high-calorie diets are in danger of becoming overweight, especially if they do not exercise regularly.

In addition to reducing red meat, saturated fat, and calorie intake, several other approaches exist for decreasing cancer hazards in the diet. One is to reduce the use of high-temperature cooking techniques, such as open flame grilling or deep frying, which generate carcinogenic polycyclic aromatic hydrocarbons and aromatic amines that were not initially present in the foods being cooked. Food preservation techniques are another potential source of dietary carcinogens that can be avoided.

For example, decreased consumption of foods that are smoked, cured, pickled, or heavily salted has been linked to a lower risk for stomach cancer. Taking simple measures to reduce pesticide contamination, such as washing or peeling fruits and veg­etables, is also a reasonable precaution, although the potential hazards of pesticide contamination are probably overemphasized.

Reducing Exposure to Carcinogens Involves a Combination of Personal and Governmental Actions:

There are two basic ways in which exposure to carcino­gens can be decreased. One is for individuals to take personal actions like those we have been discussing—that is, reducing exposure to tobacco smoke, alcohol, sunlight, ionizing radiation, cancer-causing infectious agents, and chemical carcinogens encountered in the workplace, drugs, and the diet. (Of course, people need to be edu­cated about these dangers before they can be expected to take action.) The second approach is for the government to create laws and regulations that reduce or eliminate the carcinogenic hazards to which people are exposed.

In practice, the two approaches tend to complement each other. A good illustration of this principle is provided by the history of cigarette smoking in the United States. Smoking rates increased dramatically in the twentieth century until 1964, the year in which the first Surgeon General’s Report on Smoking and Health was published (see Figure 1).

This report concluded that cigarette smoking causes lung cancer and stated, “Cigarette smoking is a health hazard of sufficient importance in the United States to warrant appropriate remedial action”. As a consequence, Congress passed the Federal Cigarette Labeling and Advertising Act of 1965 and the Public Health Cigarette Smoking Act of 1969.

These laws required health warnings on cigarette packages, restricted cigarette advertising, and called for periodic government reports on the health consequences of smoking. Over the ensuing decades a growing body of federal and local regulations imposed further controls, including restrictions on smoking in public places, airplanes, office buildings, restaurants, and the workplace.

Despite the severe health hazards involved, there has been no attempt to ban cigarettes outright, an approach that would clearly be impractical. Government and public health organizations have instead worked to educate people about the dangers of smoking and to promote a nonsmoking cul­tural environment that encourages individuals to make their own personal decision not to smoke.

This strategy has been fairly successful- Smoking rates have gradually declined over the past 40 years and people are giving up smoking in increasing numbers. In fact, nearly half of all living Amer­ican adults who ever smoked have now quit, and smoking rates among men have fallen by roughly 50% since 1964.

OSHA and the FDA are Governmental Agencies that Regulate Carcinogens in the Workplace and Food Supply:

Government involvement in protecting the public from carcinogenic hazards is not restricted to tobacco products. Another area of interest is the industrial workplace, where employees may be exposed to high doses of chemical carcinogens for prolonged periods of time.

In the first half of the twentieth century, many cancers were caused by such occupational exposures before the risks were fully appreciated. Finally, in 1970 an act of Congress created the Occupational Safety and Health Administration (OSHA) to formulate and enforce regulations that protect the safety and health of workers.

OSHA regulations have eliminated some of the most dangerous carcinogens from the workplace and have created requirements that limit worker exposure to others. As a consequence, occupational cancers that were once prevalent in the United States are declining in frequency and now account for less than 5% of all cancer deaths each year.

Regulation of carcinogens in the food supply has had a more complicated history. In the United States, food additives and contaminants that might cause cancer are regulated by the Food and Drug Administration (FDA), a federal agency whose jurisdiction includes most foods other than meat.

A law passed in 1938 empowered the FDA to prohibit the marketing of any food containing a substance that may render it injurious to health. In 1958, Congress passed the Delaney Amendment, which specifically directed the FDA to ban any food additive or contaminant if it was found to cause cancer in animals at any dose.

The Delaney Amendment, which expired in 1996, was referred to as a zero-risk standard because it allowed for no acceptance of even the tiniest amount of an additive or contaminant in food once it has been shown to exhibit any carcinogenic properties in animals.

Using the authority provided by the preceding laws, the FDA has banned a number of food additives and contaminants suspected of being human carcinogens. Among the prohibited substances are several food- coloring agents (e.g., Red No. 2 and Red No. 4), artificial sweeteners (e.g., cyclamate), and packaging materials that contaminate food (e.g., acrylonitrile used in making plastic beverage bottles). When the FDA attempted to ban the artificial sweetener saccharin, however, the difficulties inherent to its approach for assessing carcinogenic hazards became evident.

Saccharin is an artificial sweetener with a long history of use in foods and beverages. After several studies showed that saccharin causes bladder cancer in laboratory animals, the FDA proposed in 1977 to prohibit its use based on the requirements of the Delaney Amendment.

At that time, saccharin was widely used in diet foods— millions of pounds were consumed annually in soft drinks alone—and a public outcry ensued. In response, Congress passed a law overriding the FDA ban and saccharin remained legal. However, the law did require a warning label on saccharin-containing foods and beverages indicating that saccharin causes cancer in animals.

In 1981, the government used this animal evidence as justification for placing saccharin on its list of substances that are “reasonably anticipated” to be human carcinogens. Twenty years later, the government reversed its position and saccharin was removed from the list. The reason for the reversal was a series of studies showing that the original animal data, derived mainly from rats, were not likely to be relevant to humans.

The newer experiments revealed that saccharin causes bladder cancer in rats by binding to proteins in the urine, thereby triggering the formation of calcium phosphate-containing crystals that irritate the bladder wall and lead to cancer. Formation of these crystals requires the presence of high concentrations of calcium phosphate and protein in the urine, conditions unique to the rat bladder that do not exist in humans.

Regulatory Standards for Environmental Pesticides and Pollutants are Established Using Quantitative Assessments of Risks and Benefits:

The history of government efforts to regulate saccharin shows how difficult it can be to make decisions about food additives or contaminants that act as weak carcinogens in animals but may or may not cause cancer in humans. In the case of pesticides that contaminate the food supply, the situation is further complicated by the fact that different standards have been applied to raw and processed foods.

For many years pesticide contaminants detected in processed foods were considered to be additives covered by the Delaney Amendment, which imposed a standard of zero tolerance for any substance that causes cancer in animals. If the same pesticide happened to be detected in raw foods, the risk was analyzed quantitatively based on all available animal and human evidence so that an acceptable tolerance level could be established based on typical dietary intake.

Because of the confusion created by this inconsistent approach to pesticide regulation, Congress passed the Food Quality Protection Act of 1996 to eliminate the distinction between standards for raw and processed foods.

All pesticide residues are now regulated under the standard of “reasonable certainty of no harm,” which means that acceptable tolerance levels are established based on an assessment of what is thought to be safe.

Unlike the zero-tolerance standard of the Delaney Amendment, which does not discriminate between potent and weak carcinogens, the newer type of analysis establishes different tolerance levels for carcinogens of differing potency. Moreover, benefits as well as risks associated with the use of each pesticide are considered when establishing such standards.

The Environmental Protection Agency (EPA) uses a similar approach when creating regulatory standards for carcinogens that contaminate the environment. An instructive example is provided by the environmental carcinogen arsenic, which is present in trace amounts in the drinking water of many wells and municipal water systems.

Before 2001, the EPA regulatory standard for arsenic in drinking water had been set at 50 parts per billion (ppb). When epidemiological studies revealed that people who regularly drink water containing that much arsenic add about 1% to their lifetime risk of dying of cancer, the EPA proposed to lower the arsenic standard from 50 to 10 ppb.

In an ideal world, any proposal to reduce the threat from an environmental carcinogen would be immediately accepted, but in the real world of limited financial resources, the cost of each regulatory decision needs to be balanced against the benefits to be gained. It was estimated that the public and private spending required to lower the arsenic levels in drinking water from 50 to 10 ppb would range between $600,000 and $6,000,000 per avoided cancer death.

Although the EPA eventually decided that reducing arsenic levels was worth the expenditure, there is a point at which the cost of reducing the concentration of a given environmental carcinogen to a lower level becomes so great as to make the proposed effort impractical.

Since it is impossible to create a completely risk-free world in which all carcinogens have been removed, society needs to find ways of establishing priorities as to which carcinogenic hazards require the most attention. When establishing such priorities, two variables are particularly relevant. First, how potent is each carcinogen? Second, how much are we exposed to? These two variables have been combined into a single measure called the HERP value, where HERP stands for Human Exposure and Rodent Potency.

The HERP value for any given agent is calculated by determining the typical human lifetime dose of the substance in question and dividing it by the dose administered to mice or rats that causes half the animals to develop tumors within their lifetime. The HERP value is thus a measure of potential hazard that takes into account both human exposure and carcinogenic potency in animals.

In other words, powerful carcinogens with large human exposures exhibit the highest HERP values; weak carcinogens with small human exposures have the lowest HERP values, and potent carcinogens with small human exposures, or weak carcinogens with high human exposures, exhibit intermediate HERP values.

HERP calculations are not precise indicators of human hazard because of the uncertainties involved in extrapolating data on carcinogenic potency from animals to humans. Nonetheless, comparing the HERP values of various carcinogens with one another can provide insights as to which ones are likely to be most hazardous (Table 1). Such analyses have revealed that workplace exposures to chemical carcinogens tend to have high HERP values and therefore deserve considerable atten­tion.

In contrast, the pesticides and pollutants that contaminate our environment, water, and food supply generally exhibit HERP values that are quite low when compared with the background of naturally occurring carcinogens encountered in a typical diet.

Proposed Role of Fruits and Vegetables in Protecting against Cancer is Based Largely on Retrospective Studies:

During the past twenty years, the possible effectiveness of fruits and vegetables in reducing cancer risk has been investigated in more than 200 epidemiological studies. These investigations have consistently (but not univer­sally) supported the conclusion that people who eat more fruits and vegetables have lower cancer rates than people who eat fewer fruits and vegetables.

The association is strongest for cancers involving gastrointestinal and respiratory organs, such as stomach, colon, and lung cancers, and is weak for hormone-related cancers, such as breast and prostate cancers.

Unfortunately, interpreting the significance of the epidemiological evidence is complicated by two factors:

(1) The observed reductions in cancer rates are generally small, and

(2) Most of the early studies involved a retrospective approach in which people with cancer were asked to recall their previous dietary habits.

Retrospective studies are susceptible to several sources of bias and are generally less reliable than prospective studies that monitor healthy people into the future to see who develops cancer. When large prospective studies have been carried out, they generally detect little or no connection between overall fruit and vegetable consumption and cancer incidence.

This inconsistency in the epidemiological evidence has created some uncertainty regarding the precise role played by fruits and vegetables in protecting against cancer. Part of the problem may be that “fruits and vegeta­bles” is an imprecise label that includes dozens of different food items, only some of which may be useful in reducing cancer risk.

Because of the difficulty in comparing conclu­sions from different studies in which the exact food items are not clearly identified, we need to focus on individual fruits or vegetables—and the molecules they contain—to determine what roles, if any, these foods play in protecting against cancer.

Vitamins, Minerals, and Dietary Fiber are being Investigated as Possible Sources of Protection against Cancer:

A variety of natural substances present in fruits and vegetables have been investigated as possible sources of anticancer activity. Early research focused mainly on vitamins and minerals, which are known to be essential components of a healthy diet.

Vitamins A, B6, folic acid, B12, C, D, and E and the minerals calcium, iron, zinc, and selenium are among the vitamins and minerals that have been suggested to play a protective role against cancer.

Dietary intake of each of these substances has been linked to decreased cancer rates in some reports; other studies, however, have failed to confirm the results, and there is currently insufficient high-quality data to justify strong conclusions.

Further progress requires a better understanding of how vitamins and minerals exert their postulated anti­cancer effects. One property shared by several of these substances is their ability to act as antioxidants—that is, inhibitors of oxidation reactions. Carcinogenic chemicals and radiation sometimes cause DNA damage through oxi­dation reactions involving free radicals, which are atoms or molecules possessing an unpaired electron.

A free radical is a highly unstable substance that quickly attacks another nearby molecule, taking an electron that it needs to gain stability (Figure 7). Upon losing an electron, the second molecule also becomes a free radical and removes an electron from a third molecule, starting a chain reac­tion of oxidation reactions (oxidation refers to the process of losing an electron).

An uncontrolled cascade of free radical reactions can create considerable damage within a cell, including DNA mutations. Antioxidant vitamins halt this scenario by acting as free radical scavengers that donate their own electrons to free radicals without becoming unstable in the process.

For example, ascorbic acid (vitamin C) readily donates electrons to free radicals, undergoing oxidation to dehydroascorbic acid in the process. Dehydroascorbic acid is then converted back to ascorbic acid through a simple metabolic reaction and the process is repeated again.

The ability of antioxidant vitamins to function as free radical scavengers has led to the proposal that they might be able to inhibit carcinogenesis by preventing oxidative DNA damage. The principal antioxidant vitamins found in fruits and vegetables are vitamins A, C, and E.

Many retrospective studies have indicated that people who report high intake of these vitamins—either from food or through vitamin supplements—exhibit decreased cancer rates. The effects are generally small, however, and could easily be caused by other unmeasured differences in lifestyle or environment. The only way to provide convincing proof would be a randomized trial in which participants are randomly assigned to receive either a vitamin supplement or a placebo.

During the mid-1980s, a randomized trial of vitamins A and E was initiated in Finland to see whether these vita­mins can reduce lung cancer rates, as was suggested by earlier retrospective evidence. The Finnish trial involved more than 29,000 male smokers who were randomly assigned to receive vitamin A (in the form of beta-carotene), vitamin E, both, or neither (placebo).

Over a period of seven years, the trial failed to detect any protective effect of either of the two vitamins on lung cancer rates. In fact, a statistically significant increase in lung cancer cases was actually observed in the men who received vitamin A supplements (Figure 8).

A second independent study carried out in the United States confirmed the ability of vitamin A to increase lung cancer rates. Such results cast serious doubt on the usefulness of vitamin A for cancer protection and reveal the possible risks associated with using vitamins in high doses (the amounts of vitamin A employed in these studies were five to ten times higher than the normally recommended dietary intake).

The preceding results do not rule out the possibility that certain vitamins might exhibit some useful anticancer properties when consumed directly from a well-balanced diet or obtained from pills designed to deliver normally recommended vitamin doses rather than high doses. One vitamin thought to protect against cancer in normal doses is folic acid.

The typical dietary intake of folic acid in the United States is less than optimal, and low intake of folic acid can lead to DNA damage (folic acid normally provides the methyl group needed for synthesizing the base thymine in DNA). The possibility that low intake might create an increased cancer risk is supported by reports of increased colon cancer rates in people whose diets are deficient in folic acid.

In one long-term prospective study, a 75% reduction in colon cancer rates was seen in individuals who take multivitamin pills containing folic acid, although the effect did not become evident until the vitamins were used for 15 years (Figure 9).

An obvious problem in such studies is that multivitamin pills contain a variety of dif­ferent vitamins and minerals, and it is possible that ingredients other than (or in addition to) folic acid were responsible for the reduction in cancer rates. Vitamin D, for example, is thought to exert some protective effects against colon cancer and might have contributed to the observed reduction in cancer rates.

The ideal test would involve a randomized trial of folic acid or vitamin D versus placebo pills, but it is generally impractical to run trials for the long duration required in this particular case (15 years).

Vitamins are not the only constituents of fruits and vegetables for which it has been difficult to obtain reliable evidence. A similar situation exists with dietary fiber, the indigestible portion of plant foods that is composed mainly of complex polysaccharides.

Early retrospective studies suggested that colon cancer rates are decreased in people who consume large amounts of dietary fiber, but most of these studies included little information regarding other components of the diet and did not permit the effects of fiber to be clearly distinguished from the effects of other components of plant foods.

The retrospective nature of the studies also raised the possibility of numerous sources of bias, including the problem of asking individuals with cancer to recall their dietary habits from many years earlier. Large prospective studies, which tend to be more reliable, have generally found little relationship between dietary fiber intake and colon cancer protection.

It has been suggested, however, that the populations being studied do not vary sufficiently in fiber intake to detect an effect. One large prospective study of European populations, which tend to exhibit substantial variability in fiber intake, has reported that doubling the average fiber intake is associated with a 40% reduction in colorectal cancer incidence.

Fruits and Vegetables Contain Dozens of Phytochemicals that Exhibit Possible Cancer-Fighting Properties:

Although early investigations focused largely on vitamins and minerals, fruits and vegetables contain many other substances that might play roles in blocking or slowing cancer development. The collective term phytochemicals is commonly used when referring to this large group of plant-derived molecules.

Technically speaking, any chemical produced by a plant is a “phytochemical”; the term is usually restricted, however, to plant chemicals that are thought to have health-related effects but are not essential nutrients like proteins, carbohydrates, fats, minerals, and vitamins.

Phytochemicals are a structurally diverse group of molecules that exhibit a wide range of properties with potential relevance for fighting cancer. Among the most relevant properties are the abilities to inhibit carcinogen activation, stimulate carcinogen detoxification, inhibit carcinogen binding to DNA, inhibit free radical and other DNA-damaging oxidative pathways, inhibit cell prolifera­tion, inhibit oncogene expression, induce apoptosis, induce differentiation, inhibit angiogenesis, and inhibit invasion and metastasis. Laboratory studies have identified dozens of phytochemicals that might help protect against cancer through one or more of these mechanisms.

A few representative examples are illustrated in Figure 10 and briefly described below:

1. Lycopene:

Lycopene is a natural red pigment that gives tomatoes and other fruits and vegetables their reddish colors. The chemical structure of lycopene is related to that of beta-carotene (a vitamin A precursor), and, like beta- carotene, lycopene is a potent antioxidant. Epidemiological studies have linked dietary intake of lycopene, derived mainly from tomatoes and tomato-based sauces, to a reduced incidence of several cancers, especially those of the prostate, lung, and stomach.

In some cases, lycopene levels have been directly measured in blood samples to verify dietary intake. Such measurements have shown that individ­uals with higher concentrations of lycopene in their blood exhibit lower rates of cancer than people with lower concen­trations.

Lycopene’s antioxidant properties are thought to be responsible for the lowering of cancer risk, but lycopene also exerts other effects on metabolism, gene activity, and cell signaling that might be involved.

2. Isothiocyanates:

Isothiocyanates are a diverse group of compounds, characterized by the presence of a—N=C=S group, that occur in especially high concentration in the vegetable family that includes broccoli, brussels sprouts, cabbage, cauliflower, and watercress. Broccoli, for example, contains large amounts of an isothiocyanate called sulforaphane, and watercress contains large amounts of phenethyl isothiocyanate.

Isothiocyanates are potent inhibitors of tumor formation when tested in animals exposed to chem­ical carcinogens, and complete inhibition of cancer formation by relatively low doses of isothiocyanates is often observed.

The ability of isothiocyanates to block cancer development stems mainly from two properties: the ability to inhibit pathways for carcinogen activation and the ability to stimulate pathways for carcinogen detoxification. Many isothiocyanates exhibit one property or the other, and some exhibit both.

3. Epigallocatechin gallate:

Numerous animal and labora­tory experiments, along with some human epidemiological studies, have indicated a possible benefit of green tea in protecting against certain cancers, especially those of the esophagus, stomach, colon, and bladder. The substance epigallocatechin gallate (EGCG), which is present in high concentration in green tea, exhibits a number of properties that may help explain how green tea could protect against cancer.

Among these properties are the abilities of EGCG to act as an antioxidant, inhibit carcinogen activation, stimulate carcinogen detoxification, inhibit cell proliferation, induce cell cycle arrest, induce apoptosis, and inhibit angiogenesis. It remains to be determined, however, if any of these activities are exerted to a significant extent by the small amounts of EGCG a person typically ingests when drinking green tea.

4. Isoflavones:

Breast and prostate cancer rates are rela­tively low in Japan and China, where soybean-derived foods represent a significant portion of the diet. A group of soybean compounds known as isoflavones have been proposed to play a role in these reduced cancer rates. One isoflavone, called genistein, exhibits weak estrogen-like effects on the body and is therefore referred to as a phytoestrogen (“plant estrogen”).

The growth of breast cancer cells in culture is inhibited by high concentrations of genistein, suggesting that this isoflavone can act as an antiestrogen. However, at lower concentrations that may be closer to levels seen in humans who eat soy products, genistein has been reported to stimulate breast cell proliferation. Given this potential to either inhibit or stimulate breast cell proliferation, a precautionary approach to consuming soy to prevent breast cancer is advisable until the role of soy isoflavones is better understood.

5. Resveratrol:

Resveratrol, an antioxidant produced by a variety of plants, is present in especially high concentration in the skin of red grapes and in red wines made from these grapes. It has been proposed that resveratrol is responsible for the reported linkage between red wine consumption and lower death rates from cardiovascular disease and certain cancers.

In addition to acting as an antioxidant, resveratrol exhibits a number of other properties that might be relevant to cancer prevention. For example, resveratrol can promote carcinogen detoxification, inhibit DNA mutation, inhibit cell proliferation, and induce apoptosis. Resveratrol also inhibits the synthesis and metabolic activity of cyclooxygenases, which are enzymes whose role in promoting inflammation and stimulating tumor cell growth will be described shortly.

6. Sulfides:

For more than 3000 years, folklore has advocated garlic as a remedy for a variety of health problems. Recent epidemiological studies have provided some support for these beliefs by linking high levels of garlic consumption with reduced cancer rates, especially for cancers of the stomach, colon, and prostate. Garlic contains a variety of organic sulfides (compounds containing sulfur joined to carbon by single bonds) that might be relevant to the postulated benefits of garlic.

For example, a compound called diallyl sulfide, which is present in high concentration in garlic, has been shown to inhibit the development of colon, esophageal, and lung cancers in animals that have been exposed to chemical carcinogens. Organic sulfides exhibit a number of properties of potential relevance to cancer protection, including the ability to inhibit carcinogen activation, stimulate DNA repair, inhibit cell proliferation, and induce apoptosis.

The preceding list includes only a few of the numerous phytochemicals that are currently being investigated. The reported existence of cancer-preventing properties in these molecules is certainly encouraging, but a note of caution is appropriate because most investigations are still in their early stages.

For comparison purposes, it is worth pointing out that the initial body of evidence regarding the postulated role of vitamin A in preventing cancer was also very encouraging, but randomized human trials eventually revealed that the early claims were unjustified.

Since the cancer-fighting properties of phytochemicals have not been evaluated in randomized human trials, it would be premature to draw any definitive conclusions regarding their usefulness in preventing cancer.

Thus far, we have been focused on inhibiting cancer development through the use of substances present in food, either by eating specific foods or by ingesting some of the chemicals they contain, such as vitamins, minerals, and phytochemicals.

This practice of using specific chemical substances for protecting against cancer is called chemoprevention. Besides natural substances found in foods, a variety of synthetic drugs are also being explored for possible use in cancer chemoprevention efforts.

One drug known to be helpful in protecting against cancer is aspirin. The synthesis of aspirin was first reported in the late 1890s by Felix Hoffmann, a German chemist who was searching for a way to relieve his father’s arthritis pain. Motivated by folklore concerning the pain- relieving and anti-inflammatory properties of willow bark, Hoffman synthesized aspirin from an ingredient in willow bark called salicylic acid.

The ability of aspirin (acetylsalicylic acid) to reduce pain, fever, and inflamma­tion with minimal short-term toxicity has made it the world’s most widely used medication. Aspirin works by inhibiting the enzyme cyclooxygenase (COX), which catalyzes the production of chemical messengers called prostaglandins.

Some prostaglandins act on blood vessels, nerves, and cells of the immune system to trigger tissue inflammation, which is characterized by swelling, redness, pain, and heat. By inhibiting cyclooxygenase, aspirin reduces prostaglandin production and thereby diminishes these symptoms.

During the 1990s, a series of retrospective and prospective epidemiological studies revealed that people who use aspirin on a regular basis exhibit up to a 50% reduction in colon cancer rates. Lower rates for several other types of cancer were reported as well, including cancers of the prostate, lung, mouth, throat, and esophagus.

Such results suggest that aspirin might be a simple and effective tool for cancer chemoprevention. Unfortunately, chronic use of aspirin has drawbacks because the drug also causes stomach irritation, bleeding, and ulcers. The reason for these side effects is that cyclooxygenase, the enzyme inhibited by aspirin, exists in multiple forms with differing functions.

One form, called COX-1, is expressed in many cell types and plays a variety of normal roles, such as protecting the lining of the stomach against acid irritation. Inhibition of COX-1 by aspirin interferes with this protective function, thereby triggering the adverse effects of aspirin on the stomach.

A second form of cyclooxygenase, called COX-2, is also inhibited by aspirin. Normal tissues contain relatively little COX-2 but production of the enzyme is enhanced at sites of tissue damage, where it synthesizes prostaglandins that trigger tissue inflammation. COX-2 is also produced by colon cancers and other epithelial malignancies, where it may contribute to tumor development by synthesizing a prostaglandin known as prostaglandin E2 (PGE2).

PGE2 exhibits several properties that could help cancer cells proliferate, survive, and evade the immune system. First, PGE2 inhibits the activity of cytotoxic T lymphocytes, which might otherwise attack tumor cells. PGE2 also stimulates angiogenesis, which is required for tumor growth beyond a tiny size, and it inhibits apoptosis in cancer cells. Each of these properties could play a role in cancer development and progression.

The discovery that COX-2 produces prostaglandins that trigger tissue inflammation and facilitate cancer development suggests that aspirin’s ability to decrease cancer risk stems from its inhibitory effects on COX-2. Aspirin’s adverse effects, such as stomach bleeding and ulcers, are linked to its inhibition of COX-1.

To obtain the beneficial effects of aspirin without the adverse side effects, several new anti-inflammatory drugs were intro­duced in the late 1990s that selectively inhibit COX-2 rather than inhibiting both COX-1 and COX-2 like aspirin does.

These selective COX-2 inhibitors, sold under the trade names Vioxx, Celebrex, and Bextra, were initially introduced to provide relief from chronic arthritis pain without causing the stomach problems seen with aspirin.

Preliminary evidence suggested that COX-2 inhibitors might also be useful for reducing colon cancer risk, and a large clinical trial was initiated in early 2000. Unfortunately, the trial was halted in late 2004 when it was discovered that COX-2 inhibitors double the risk of heart attack and stroke, and the future of these drugs is now uncertain.

Several other anti-inflammatory drugs in addition to aspirin—for example, acetaminophen (Tylenol) and ibuprofen—have also been reported to exhibit some protective effects against cancer, although the data are not nearly as extensive as for aspirin. The possible usefulness of these and other anti-inflammatory drugs for reducing cancer risk is likely to be an area of active future investigation.

Hormone-Blocking Drugs are Potentially Useful for Preventing Hormone-Dependent Cancers:

Cancers arising in hormone-dependent tissues, such as the breast and prostate, are sometimes treated with drugs that interfere with the actions of the required hormones. For example, tamoxifen blocks the estrogen receptors of breast cells and inhibits the ability of estrogen to drive the prolif­eration of these cells, thereby making the drug useful for treating estrogen-dependent breast cancers.

Tamoxifen may also be helpful for preventing breast cancer in women at high risk for the disease. The rationale for this approach is related to events that normally control the proliferation of breast cells. During each menstrual cycle, estrogen triggers the proliferation of epithelial cells that line the milk glands in the breast.

If pregnancy does not occur, estrogen levels decline at the end of the men­strual cycle and those breast cells that have proliferated in that month deteriorate and die. For the average woman, the result is hundreds of cycles of cell division and death repeated over a span of roughly 40 years, from puberty to menopause.

These repeated cycles of estrogen-induced cell division increase the risk of developing cancer in two ways:

(1) Estrogen stimulates the division of any cells that may have already acquired DNA mutations, thereby increasing the number of mutant cells that might progress to malignancy; and

(2) Repeated cycles of estrogen-induced proliferation increase the chances of new mutations arising as a result of errors in DNA replication.

Because estrogen-driven proliferation of breast cells increases the risk of cancer, using tamoxifen to block estrogen action would be expected to lower the cancer risk. To test this hypothesis, the National Cancer Insti­tute sponsored a study during the 1990s that involved more than 13,000 healthy women considered to be at high risk for breast cancer based on either their family or medical history.

Half the women were given tamoxifen and the other half were given a placebo. Over a five-year period, the women receiving tamoxifen experienced a roughly 50% reduction in new cases of breast cancer (Figure 11).

If a reduction in breast cancer risk were the only effect of tamoxifen, the drug would be widely recommended for breast cancer prevention. Unfortunately, tamoxifen has a side effect that limits its usefulness. This side effect arises because tamoxifen does not block estrogen receptors in every tissue as it does in the breast.

In the uterus, tamoxifen mimics the action of estrogen when it binds to estrogen receptors; thereby stimulating cell proliferation and increasing the risk of uterine endometrial cancer (see Figure 11, right). Tamoxifen is therefore unsuitable as a cancer prevention drug in women with no obvious sus­ceptibility to breast cancer because of the elevated risk of developing uterine cancer.

Drugs like tamoxifen, which block estrogen action in some tissues but act like an estrogen in others, are called selective estrogen receptor modulators (SERMs) because they selectively stimulate or inhibit the estrogen receptors of different target tissues. Scientists have been working to develop other SERMs that might exhibit the beneficial properties of tamoxifen on the breast without its harmful effects on the uterus.

One example is raloxifene, a drug that is useful for preventing osteoporosis (bone loss) in postmenopausal women. Raloxifene functions like estrogen in bone, acting to maintain bone strength and increase bone density.

In contrast, raloxifene blocks estrogen action in the breast and uterus and has been shown to reduce the incidence of breast and uterine cancers in animal studies. The National Cancer Institute is therefore sponsoring a human trial called the Study of Tamoxifen and Raloxifene (STAR) to directly compare the effects of the two drugs in preventing cancer.

Prostate cancer is another type of cancer arising in a hormone-dependent tissue that might be preventable using drugs that block hormone action. Since the proliferation of prostate cells depends on steroid hormones called androgens (testosterone is one example), prevention efforts have focused on drugs that inhibit androgen activity.

One such drug, finasteride, is an enzyme inhibitor that blocks the production of dihydrotestosterone, the active form of testosterone in the prostate. In a randomized trial involving more than 18,000 men, daily use of finasteride was found to reduce the incidence of new cases of prostate cancer by 25% compared with the placebo group.

While these results suggest that hormonal prevention of prostate cancer might be an attainable goal, there are significant concerns about the use of finasteride for this purpose. The most serious problem is the discovery that men receiving finasteride in the randomized trial developed a higher proportion of high-grade cancers (37% of their tumors were high grade) than did the men who received the placebo (22% of their tumors were high grade).

So even though men receiving finasteride developed fewer cancers, the tumors that did develop were more aggressive on average than those observed in the control group. One possible explanation for this unex­pected result is that the androgen-deficient environment created by finasteride treatment may favor the develop­ment of tumors that are more aggressive because they do not depend on androgens for their growth.

Whatever the correct explanation turns out to be, concerns about the high incidence of aggressive cancers makes it inappro­priate to recommend finasteride for routine use as a cancer prevention agent.

A Healthy Body Weight and Regular Physical Exercise can Reduce Cancer Risks:

It has been known for many years that individuals who are overweight have a higher-than-normal incidence of several types cancer, mainly uterine, breast, and colon cancers. Only recently has it become apparent that the impact of being overweight is much broader than this.

In 2003, the American Cancer Society published a study in which body weight and cancer death rates were tracked in more than 900,000 people for 16 years. The data revealed that obesity is linked to increased death rates for cancers of the uterus, breast, colon, esophagus, pancreas, kidney, gallbladder, ovary, liver, and prostate, as well as cancers of blood cells such as multiple myeloma and non-Hodgkin’s lymphoma.

To determine who was overweight, these studies estimated the amount of body fat each person carries using a formula based on height and weight called the Body Mass Index (BMI):

Although this formula tends to overestimate body fat in muscular individuals, people are generally considered to be overweight if their BMI is 25 or higher and obese if it is 30 Of higher, When the BMI was used to assess body weight in the American Cancer Society study, a direct relationship was detected between the amount of excess weight a person carries and a progressively greater risk of dying of cancer (Figure 12).

The linkage between cancer and excess body weight is especially troubling because a growing epidemic of obesity has been occurring in the United States since the early 1980s. By the year 2000, roughly 60% of U.S. adults were categorized as being overweight or obese, putting more than 100 million people at increased risk for dying of cancer (Figure 13).

Because the American Cancer Society study measured cancer death rates, its conclusions reflect the combined influence of body weight on both the risk of developing cancer and survival rates after diagnosis. How does excess body weight exert its negative influence on these events?

Several mechanisms are thought to be involved, but a central element appears to be the tendency of obesity to raise circulating levels of insulin, estrogen, and other growth-stimulating hormones. Such molecules can con­tribute to the promotion phase of carcinogenesis by stimulating cell proliferation and may also stimulate tumor growth after cancer has arisen.

There are two ways of avoiding the accumulation of excess body weight that leads to increased cancer risk. One is to eat a diet that does not contain too many calo­ries, and the other is to engage in regular physical exercise. Exercise plays an especially important role because its effects on cancer risk are not limited to main­taining a healthy body weight.

When individuals of the same exact weight are compared with one another, those who are physically active still have lower cancer rates than those who are inactive. One possible explanation is that individuals who exercise regularly tend to have more muscle tissue and less body fat than individuals of the same weight who do not exercise, and reduced levels of body fat are associated with hormonal and metabolic changes that may reduce cancer risks. Exercise-induced stimulation of immune function and antioxidant path­ways has also been reported, but the relevance of these changes (if any) to the development of cancer remains to be determined.

Vaccines and Antibiotics are Useful for Preventing Cancers Caused by Viruses and Bacteria:

The importance of avoiding exposure to cancer-causing infectious agents—such as human papillomavirus, hepatitis B virus, hepatitis C virus, and the bacterium H. pylori. Complete avoidance, however, is extremely difficult because of the widespread prevalence of these infectious agents. It is therefore important to pursue approaches for preventing cancer from arising in people who have already been exposed.

One strategy is the development of vaccines that immunize against cancer-causing infectious agents. In the case of the hepatitis B virus, effective vaccines have been available since 1982.

Many countries now include hepatitis B vaccination in their routine childhood immunization programs, and reduced liver cancer rates have already been reported in immunized individuals. Developing a vaccine for hepatitis C has taken longer because the hepatitis C virus exhibits greater genetic variability, but candidate vaccines are currently being developed and evaluated.

Vaccination against human papillomavirus (HPV), the main cause of cervical cancer, is also being actively pursued. Creating a vaccine that protects against HPV is not a straightforward task because more than 100 different types of HPV exist and roughly a dozen have been implicated in the development of cancer. HPV 16 was the first to be pursued as a vaccine target because it is the most common strain of HPV in invasive cervical cancers, occurring in more than 50% of such tumors.

In 2002, results from the first successful trial of an HPV 16 vaccine were reported in a study involving more than 2300 women. The vaccine was found to be 100% effective in preventing HPV 16 infection and cervical cancer over a period of two years. Preliminary testing of another vaccine, which includes protection against HPV 18 as well as HPV 16, has also been successful, and it is anticipated that these vaccines will soon meet FDA requirements for general use.

Finally, H. pylori is one of the most common disease- causing microbes worldwide, infecting roughly two-thirds of the global population. Efforts to prevent stomach cancer caused by chronic infection with this bacterium are being pursued in two different ways. First, a vaccine designed to block persistent infection with H. pylori has been developed and is currently undergoing human testing.

In addition, the fact that H. pylori is a bacterium rather than a virus makes it susceptible to treatment with antibiotics. When antibiotics are administered to infected individuals early in the course of infection to rid them of H. pylori, the risk of stomach cancer is dramatically reduced.