(1)
Daytona Beach Shores, FL, USA
Scientists plan to check toenail clippings from hundreds of people in Garfield, New Jersey, to determine if residents were exposed to a toxic metal linked to lung cancer.
– Reuters, March 25, 2013
4.1 First the Basics
Cancer is caused by hereditary factors and by environmental carcinogens. While the former are currently inescapable, the later are potentially preventable. A carcinogen is any substance or agent in the environment that, through genotoxic or non-genotoxic mechanisms, leads to cancer. Because ethical issues preclude prospective studies on the ill effects of agents suspected to be harmful to humans, evidence for assessing their carcinogenicity must rely on indirect studies. The most reliable are epidemiological studies (cohort, case-control, correlation, intervention studies) to which biomarkers data are included whenever available. Because these types of studies do not necessarily yield clear answers, agents studied have been classified as known, probably, or possibly carcinogenic to humans. Known carcinogens include lifestyle factors (e.g. tobacco use), exposure to non-infectious agent such as natural elements (e.g., ultraviolet light, radon gas), medical treatments (e.g. chemotherapy and radiotherapy), workplace exposure (e.g., asbestos), household exposure (e.g. formaldehyde in air fresheners), air pollution (e.g. diesel exhaust) and infectious agents (e.g. hepatitis B virus and human papilloma virus). According to the International Agency for Research on Cancer (IARC), there were 109 known (Group 1), 65 probable (Group 2A), and 275 possible (Group 2B) agents carcinogenic to humans, as of July 2013 [243]. However, because several national and international agencies study different agents at different times, lists of carcinogens, their composition, and agent carcinogenicity do not necessarily match.
The cancer-carcinogen link is highly variable, depending mostly on the intrinsic carcinogenicity of each agent, the amount and duration of exposure, and the individual’s susceptibility to a particular agent. For instance, only a minority of tobacco smokers develops cancer and does so after many years of heavy exposure. In contrast, prolonged exposure to bis(chloromethyl) ether (BCME) either through inhalation or skin contact increases the risk of lung cancer up to ten-fold and the heavier the exposure the shorter the time to diagnosis. In addition, the type of cancer resulting from carcinogenic exposure depends on tissue susceptibility. For instance, while the IARC identifies 15 agents associated with lung cancer, radioactive iodide induces almost exclusively thyroid cancer. The contribution of environmental carcinogens to cancer is not negligible. Indeed, “In the industrialized nations, roughly 7 % of cancer deaths are attributable to viral infections; 4 % to occupational hazards; 2 % to sunlight; 2 % to pollutions of air, water, and soil; and less than 1 % to food additives and industrial products” [244, 245]. Indeed, it is estimated that 90–95 % of all cancers have roots in the environment, if lifestyles are included [246]. Indeed, although the National Institute for Occupational Safety and Health (NIOSH) estimates approximately 20,000 yearly deaths from occupational cancers in the US (mostly lung and bladder cancer, and mesothelioma), “the estimated percentage of cancers related to occupational and environmental carcinogens is small compared to the cancer burden from tobacco smoking (30 %) and the combination of poor nutrition, physical inactivity, and obesity (35 %)” [247]. Hence, while approximately 15 % of cancers in the US are caused by unintended daily exposure to a mixture of occupational, household, and other industrial carcinogens, the rest are caused by well-known and easier to control risky lifestyles. Yet, after highlighting asbestos and seven other chemical carcinogens, the President’s Cancer Panel report (2010) advocated a new prevention-oriented chemicals policy, strongly urging the President “to use the power of your office to remove the carcinogens and other toxins from our food, water, and air that needlessly increase health care costs, cripple our Nation’s productivity, and devastate American lives.” Risky health behavior as the leading cause of cancer is not restricted to the US. Indeed, according to the WHO,
About 30 % of cancer deaths are due to the five leading behavioral and dietary risks…Tobacco use is the most important risk factor for cancer causing 22 % of global cancer deaths…[and] Cancer causing viral infections such as HBV/HCV and HPV are responsible for up to 20 % of cancer deaths in low- and middle-income countries [248].
The following section briefly addresses common underlying mechanisms of carcinogens leading to cancer, but focuses on the three risky lifestyles that together account for several times more cancers in the US than all other environmental carcinogens combined and are much less challenging to prevent and control. Indeed, only a small fraction of the thousands of chemicals released into the environment by industry have been studied after several decades of efforts by the IARC, the National Institute for Occupational Safety and Health (NIOSH), and other specialized agencies in several countries. Hence, it is utterly unrealistic to expect the control of unintended and unsuspected exposure to thousands of potentially carcinogenic environmental agents, as well as the assessment of their individual carcinogenicity, especially because new untested and uncontrolled substances are released into the environment each day, and most contribute to the betterment of modern life. The most rational and efficient approach for reducing the impact of carcinogens on the population is to focus on three lifestyles that together account for approximately two thirds of all cancers in the US, as will be highlighted in the next segment.
4.2 More Details
Carcinogenicity is a highly complex and evolving field, involving epigenetic phenomena and miRNA that is still froth with uncertainties, including the recent surprising finding that “Shiftwork that involves circadian disruption is ‘probably carcinogenic to humans’” [249]. Suffice it to say that while the vast majority of carcinogens exert their effects via DNA damage (e.g. are genotoxic), a substantial number are non-genotoxic, accounting for 12 % (45/371) of IARC’s Groups 1, 2A and 2B carcinogens with 27 % (12/45) posing a “potential hazard” [250]. Prior to becoming genotoxic, most chemical carcinogens must be activated by cytochrome P450 enzymes. Yet, the same P450 enzymes also metabolize and inactivate chemicals. Hence, the balance between activation and deactivation will determine whether a chemical becomes carcinogenic. On the other hand, non-genotoxic carcinogens have been shown to act as,
Additionally, except for carcinogens that can easily be studied in isolation, such as tobacco, most exposures are to mixtures of very diverse agents arising from multiple sources, making it difficult to assess the carcinogenicity and assign causality of single agents. Hence, given the sheer number of potential carcinogens and the colossal task needed to remove them from the environment, I will concentrate on three lifestyles linked to cancer that, in contrast to unintended exposure to environmental carcinogens, result from individual choice and are linked to approximately 2/3 of all cancers in the US. This crucial difference in the source of exposure to carcinogens empowers involved individuals to control their own exposure via behavior modification rather than relying on governmental regulation or industry goodwill that are retro- rather than pro-active at best.
…tumor promoters (e.g. 1,4-dichlorobenzene), endocrine-modifiers (e.g. 17beta-estradiol), receptor-mediators (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin), immune suppressors (e.g. cyclosporine), or inducers of tissue-specific toxicity and inflammatory responses (e.g. arsenic and beryllium) [251].
According to the Center for Disease Control and Prevention (CDC), the three leading causes of mortality in the U.S. are preventable, self-inflicted diseases. In a recent press release it reported, “The leading causes of death in 2000 were tobacco (435,000 deaths; 18.1 % of total US deaths), poor diet and physical inactivity (400,000 deaths; 16.6 %), and alcohol consumption (85,000 deaths; 3.5 %)” [252]. Additionally, ultraviolet radiation from the sun or artificial sources account for most cases of skin cancers, especially melanoma. Indeed, as the popularity of natural and artificial tanning rose through the 1980s and 1990s, incidence rates for melanoma in the US rose from 8.7/100,000 in 1975 to 28/100,000 in 2009, the fifth most frequent cancer after colorectal cancer [253]. Hence, while it is estimated that 19 % of all cancers worldwide are caused by unintended exposure to difficult to prevent or control environmental and occupational carcinogens [254], efforts at behavior modification at the national, state, and health care provider levels should focus on education designed to avoid what in essence are self-inflicted diseases caused by risky lifestyles. While lifestyle behavior modification is a long and difficult albeit overdue course of action, an incentivized healthcare payment model should be at its core [255].
4.2.1 Smoking
Since the Surgeon General’s 1964 “Report on Smoking and Health” that alerted the nation to the health risk of smoking, the direct causal relationship between tobacco use and cancer has been periodically revisited and confirmed. In its 2004 report, the Surgeon General extended the tobacco-cancer link to include cancer of the lung, larynx, oral cavity and pharynx, esophagus, stomach, pancreas, kidney and renal pelvis, urinary bladder, and cervix, and AML [256]. The IARC also studied the tobacco-cancer link in 1986 and 2002 and, although the methodology used was somewhat different, its conclusions were similar [257]. In 2012, smoking accounted for approximately 85 % of 205,974 cases of lung cancers in the United States including 3,400 from secondhand exposure, which is the second leading cause of death among men and women. A recent study of mortality trends across three time periods (1959–1965, 1982–1988, and 2000–2010) among participants 55 years of age or older found a 2.73, 12.65, and 25.66 relative risks of death from lung cancer, respectively, for women current smokers and 12.22, 23.81, and 24.97 for male smokers, compared to their respective nonsmokers counterparts [258]. In 2012, lifelong male and female smokers were 23 and 13 times more likely to develop lung cancer than nonsmokers, respectively [259], despite a 54 % drop in the smoking population since 1965, as shown in Fig. 4.1. The CDC also reported 5.1 Ma of Years of Potential Life Lost (YPLL) annually linked to smoking in the United States between 2000 and 2004. The health effects of smoking are not surprising, given the more than “7,000 chemicals, including hundreds that are toxic and about 70 that can cause cancer” [260].
Fig. 4.1
Smoking trends by sex and race between 2005 and 2010
Lung cancer is the second leading cause of death in the US. Yet, private and public economic interests dictate our ambivalent national policy on tobacco that fails to dissuade potential smokers, as shown by the following statistics [261].
While the benefits of avoiding environmental carcinogens are real but difficult to assess, smoke cessation accrues enormous benefits when successful, as shown by indisputable empirical evidence. Indeed, according to the Surgeon General “when smokers quit the risk for a heart attack drops sharply after just 1 year; stroke risk can fall to about the same as a nonsmoker’s after 2–5 years; risks for cancer of the mouth, throat, esophagus, and bladder are cut in half after 5 years; and the risk for dying of lung cancer drops by half after 10 years” [263].
In 2010, the cigarette industry spent $8.05 billion to promote smoking.
In 2013, states will collect $25.7 billion from tobacco taxes and legal settlements, but will spend less than 2 % of that sum on tobacco control programs.
In 2010, 43.8 million Americans (19.0 % of all adults) smoked.
Nearly 20 % of young adults ages 19–28 smoke daily and 12.5 % smoke half a pack or more each day [262].
Each day, over 3,600 persons younger than 18 years of age smoke their first cigarette.
In 2010, cigarette smoking cost the nation more than $193 billion ($97 billion in lost productivity plus $96 billion in health care expenditures).
4.2.2 Obesity
Overeating and lack of exercise have become a health problem in industrialized and underdeveloped countries alike. In the US, the prevalence of obesity1 in adults age 20–74 rose from 15 % in the 1976–1980 period to 35 % in 2005–2006. Overweight2 affects 15 % of children and 18 % of adolescents. More disturbingly, 11 % of infants, ages 2–5 were overweight in 2005–2006, most of whom will become obese adults [264]. The numbers of adult smokers declined by 18.5 % between 1993 and 2008, whereas the proportion of obese people increased 85 %. Between 1973 and 2008, healthy weight American adults decreased from 50 to 30 % whereas the number of obese rose from 14 to 37 % (Fig. 4.2). Like smoking, overweight and obesity lead to profound and costly health consequences in terms of human suffering and economic costs. Indeed, they are associated with an increased risk of coronary artery disease, type-II diabetes, hypertension, stroke, liver and gallbladder disease, sleep apnea, osteoarthritis, gynecological problems (e.g., infertility), and cancer (e.g., endometrial, kidney, and colon, among others) [265]. The risk of some cancers increases with increasing weight. Table 4.1 shows the relative risk of cancer in obese persons and the percentage of cancer attributable to obesity (CAO) within that population. Given the number of chronic diseases associated with obesity, its long-term effect on healthcare costs is enormous. For instance, it has been estimated that between 1987 and 2001, inflation-adjusted per capita spending for heart disease and diabetes in overweight people was 41 %, and 38 % higher, respectively, than for people of normal weight. Overall, the estimated cost of overweight and obesity was $147 billion in 2009 [266].
Fig. 4.2
Percentage of adults age 20–74 who were at a Healthy weight (◾), Overweight (⚫), and Obese (▴): 1971–2008 (Reproduced from National Center for Human Statistics. National Health and Nutrition Examination Survey)
Type of cancer | Relative riska | CAO (%) |
|---|---|---|
Endometrial | 3.5 | 57 |
Esophageal | 3.0 | 52 |
Kidney | 2.5
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