Tobacco and Cancer: Recent Epidemiological Evidence

Abstract

During the 1950s, the evidence was clearly sufficient to establish the carcinogenicity of tobacco smoking (1). By the end of the 1950s, convincing evidence linking smoking with lung cancer and other cancers had been obtained from case–control and cohort studies, carcinogens had been identified in tobacco smoke, and cigarette smoke condensate had been shown to cause tumors when painted on the skin of mice. Since then, the numbers of deaths attributable to tobacco smoking have sharply increased, reflecting the heavy smoking patterns of previous decades. It has been estimated that tobacco smoking is currently responsible for approximately 30% of all cancer deaths in developed countries, and that if current smoking patterns persist, an epidemic of cancer attributable to tobacco smoking is expected to occur in developing countries (2). In addition, smoking causes even more deaths from vascular, respiratory, and other diseases than from cancer, so that, in total, tobacco smoking is estimated to account for approximately 4–5 million deaths a year worldwide. This number is projected to increase to approximately 10 million a year by 2030. Thus, if current smoking patterns continue, there will be more than 1 billion deaths attributable to tobacco smoking in the 21st century compared with approximately 100 million deaths in the 20th century (2). The only other causes of disease with such rapidly increasing impact are those associated with human immunodeficiency virus infection and, perhaps, obesity in Western countries (2). In this commentary, we review the evidence regarding the carcinogenicity of tobacco smoke that has accumulated during the last 16 years since the publication of Monograph 38 of the International Agency for Research on Cancer (IARC) in 1986 (3) to the updating of that monograph (Monograph 83) in 2002 (4). The evidence now available shows that tobacco smoke is a multipotent carcinogenic mixture that can cause cancer in many different organs. In addition, exposure to secondhand tobacco smoke (i.e., involuntary or passive smoking by persons who do not smoke) is also carcinogenic for the human lung. This commentary, written by the epidemiologists who participated in the 2002 IARC Working Group for the preparation of the IARC Monograph 83 (4), is based on the substantial body of evidence reviewed for that purpose. It represents, however, solely the views of the authors. In 1986, the IARC Working Group (3) found that there was sufficient evidence that active tobacco smoking was carcinogenic in humans, and concluded that tobacco smoking caused cancers not only of the lung, but also of the lower urinary tract including the renal pelvis and bladder; upper aero-digestive tract including oral cavity, pharynx, larynx, and esophagus; and pancreas. The assessment of the evidence was based on well-established principles for evidence evaluation and an application of criteria of causality. These principles include consideration of lack of any bias or plausible confounding factors that could explain the observed associations, strength of association, dose–response relationships, biologic plausibility, and the consistency of findings across investigations, study designs, and countries. The criteria used by the 2002 IARC Working Group for causality assessment are described in Table 1. Cancer can be caused by smoking cigarettes, pipes, cigars, or bidis (which consist of a small amount of tobacco wrapped in the leaf of another plant, and are commonly used in South Asia). Since 1986, further evidence has been published that showed that smoking tobacco can also cause cancer of the nasal cavity, paranasal sinuses, and nasopharynx; stomach; liver; kidney; cervix uteri; and adenocarcinoma of the esophagus and myeloid leukemia. We consider the currently available evidence equivocal for cancer of the large bowel. The evidence was found to weigh against causality for cancer of the breast, in agreement with a recent meta-analysis (5), and for cancer of the prostate (6,7). For both breast and prostate the average relative risk is approximately 1.0, the positive studies do not outweigh the negative studies in overall quality, and biologic plausibility is weak. We found that the evidence suggested an inverse relationship of tobacco smoking with endometrial cancer (8). In this commentary, we briefly review the evidence that underlies the conclusions of the 2002 IARC Working Group, and summarize the numbers of studies available and the order of magnitude of relative risks for each site with sufficient evidence of carcinogenicity (Table 2). The following site-specific sections are for those sites for which we now believe there to be sufficient evidence, since the 1986 monograph (3), to conclude that smoking is a cause of cancer. (Note: although much of the evidence is based on cigarette smoking, many of the papers also contained information on other forms of tobacco smoking. Consequently, we use the generic term “tobacco” to include al