Abstract
This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes.
INTRODUCTION
After sequencing his own genome, pioneer genomic researcher Craig Venter remarked at a leadership for the twenty-first century conference, “Human biology is actually far more complicated than we imagine. Everybody talks about the genes that they received from their mother and father, for this trait or the other. But in reality, those genes have very little impact on life outcomes. Our biology is way too complicated for that and deals with hundreds of thousands of independent factors. Genes are absolutely not our fate. They can give us useful information about the increased risk of a disease, but in most cases they will not determine the actual cause of the disease, or the actual incidence of somebody getting it. Most biology will come from the complex interaction of all the proteins and cells working with environmental factors, not driven directly by the genetic code” (http://indiatoday.digitaltoday.in/index.php?option=com_content&task=view&isseid=48&id=6022§ionid=30&Itemid=1).
This statement is very important because looking to the human genome for solutions to most chronic illnesses, including the diagnosis, prevention, and treatment of cancer, is overemphasized in today’s world. Observational studies, however, have indicated that as we migrate from one country to another, our chances of being diagnosed with most chronic illnesses are determined not by the country we come from but by the country we migrate to (1–4). In addition, studies with identical twins have suggested that genes are not the source of most chronic illnesses. For instance, the concordance between identical twins for breast cancer was found to be only 20% (5). Instead of our genes, our lifestyle and environment account for 90–95% of our most chronic illnesses.
Cancer continues to be a worldwide killer, despite the enormous amount of research and rapid developments seen during the past decade. According to recent statistics, cancer accounts for about 23% of the total deaths in the USA and is the second most common cause of death after heart disease (6). Death rates for heart disease, however, have been steeply decreasing in both older and younger populations in the USA from 1975 through 2002. In contrast, no appreciable differences in death rates for cancer have been observed in the United States (6).
By 2020, the world population is expected to have increased to 7.5 billion; of this number, approximately 15 million new cancer cases will be diagnosed, and 12 million cancer patients will die (7). These trends of cancer incidence and death rates again remind us of Dr. John Bailer’s May 1985 judgment of the US national cancer program as a “qualified failure,” a judgment made 14 years after President Nixon’s official declaration of the “War on Cancer.” Even after an additional quarter century of extensive research, researchers are still trying to determine whether cancer is preventable and are asking “If it is preventable, why are we losing the war on cancer?” In this review, we attempt to answer this question by analyzing the potential risk factors of cancer and explore our options for modulating these risk factors.
Cancer is caused by both internal factors (such as inherited mutations, hormones, and immune conditions) and environmental/acquired factors (such as tobacco, diet, radiation, and infectious organisms; Fig. 1). The link between diet and cancer is revealed by the large variation in rates of specific cancers in various countries and by the observed changes in the incidence of cancer in migrating. For example, Asians have been shown to have a 25 times lower incidence of prostate cancer and a ten times lower incidence of breast cancer than do residents of Western countries, and the rates for these cancers increase substantially after Asians migrate to the West (http://www.dietandcancerreportorg/?p=ER).
Fig. 1.
The importance of lifestyle factors in the development of cancer was also shown in studies of monozygotic twins (8). Only 5–10% of all cancers are due to an inherited gene defect. Various cancers that have been linked to genetic defects are shown in Fig. 2. Although all cancers are a result of multiple mutations (9, 10), these mutations are due to interaction with the environment (11, 12).
Fig. 2.
These observations indicate that most cancers are not of hereditary origin and that lifestyle factors, such as dietary habits, smoking, alcohol consumption, and infections, have a profound influence on their development (13). Although the hereditary factors cannot be modified, the lifestyle and environmental factors are potentially modifiable. The lesser hereditary influence of cancer and the modifiable nature of the environmental factors point to the preventability of cancer. The important lifestyle factors that affect the incidence and mortality of cancer include tobacco, alcohol, diet, obesity, infectious agents, environmental pollutants, and radiation.
RISK FACTORS OF CANCER
Tobacco
Smoking was identified in 1964 as the primary cause of lung cancer in the US Surgeon General’s Advisory Commission Report (http://profiles.nlm.nih.gov/NN/Views/AlphaChron/date/10006/05/01/2008), and ever since, efforts have been ongoing to reduce tobacco use. Tobacco use increases the risk of developing at least 14 types of cancer (Fig. 3). In addition, it accounts for about 25–30% of all deaths from cancer and 87% of deaths from lung cancer. Compared with nonsmokers, male smokers are 23 times and female smokers 17 times more likely to develop lung cancer (http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts_and_Figures_2008.asp accessed on 05/01/2008). The carcinogenic effects of active smoking are well documented; the U. S. Environmental Protection Agency, for example, in 1993 classified environmental tobacco smoke (from passive smoking) as a known (Group A) human lung carcinogen (http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=2835 accessed on 05/01/2008). Tobacco contains at least 50 carcinogens. For example, one tobacco metabolite, benzopyrenediol epoxide, has a direct etiologic association with lung cancer (14). Among all developed countries considered in total, the prevalence of smoking has been slowly declining; however, in the developing countries where 85% of the world’s population resides, the prevalence of smoking is increasing. According to studies of recent trends in tobacco usage, developing countries will consume 71% of the world’s tobacco by 2010, with 80% increased usage projected for East Asia (http://www.fao.org/DOCREP/006/Y4956E/Y4956E00.HTM accessed on 01/11/08). The use of accelerated tobacco-control programs, with an emphasis in areas where usage is increasing, will be the only way to reduce the rates of tobacco-related cancer mortality.
Fig. 3.
How smoking contributes to cancer is not fully understood. We do know that smoking can alter a large number of cell-signaling pathways. Results from studies in our group have established a link between cigarette smoke and inflammation. Specifically, we showed that tobacco smoke can induce activation of NF-κB, an inflammatory marker (15,16). Thus, anti-inflammatory agents that can suppress NF-κB activation may have potential applications against cigarette smoke.
We also showed that curcumin, derived from the dietary spice turmeric, can block the NF-κB induced by cigarette smoke (15). In addition to curcumin, we discovered that several natural phytochemicals also inhibit the NF-κB induced by various carcinogens (17). Thus, the carcinogenic effects of tobacco appear to be reduced by these dietary agents. A more detailed discussion of dietary agents that can block inflammation and thereby provide chemopreventive effects is presented in the following section.
Alcohol
The first report of the association between alcohol and an increased risk of esophageal cancer was published in 1910 (18). Since then, a number of studies have revealed that chronic alcohol consumption is a risk factor for cancers of the upper aerodigestive tract, including cancers of the oral cavity, pharynx, hypopharynx, larynx, and esophagus (18–21), as well as for cancers of the liver, pancreas, mouth, and breast (Fig. 3). Williams and Horn (22), for example, reported an increased risk of breast cancer due to alcohol. In addition, a collaborative group who studied hormonal factors in breast cancer published their findings from a reanalysis of more than 80% of individual epidemiological studies that had been conducted worldwide on the association between alcohol and breast cancer risk in women. Their analysis showed a 7.1% in