Tobacco Documents Online

A Scientific Perspective The Tobacco Institute 1875 1 Street, Northwest Washington, D.C. 20006

..~ . ... .•.a.. ...•h.~..._....w..1....n..........w:w .... . .... e.......w..a..-. l..i....n.... .~... Summary of Contents Overvi ew . . . . . . . . . . . . . . . . . . . . . . . . . . page 1 Cancer of the Lung . . . . . . . . . . . . . . . . . . . . . page 1 1 The assertion that cigarette smoking is the cause of lung cancer ignores basic, unresolved questions about laboratory data, smoking patterns and mortality rates, diagnostic var- iations and other confounding factors. Cancer of the Esophagus . . . . . . . . . . . . . . . . . . page 33 Interpretation of a statistical relationship between smoking and esophageal cancer must involve considerable guesswork, because the association is inconsistent on a worldwide basis and among Western nations. Cancer of the Larynx . . . . . . . . . . . . . . . . . . . page 39 Data do not warrant a conclusion that smoking causes laryngeal cancer: Population studies provide insufficient information, and disease patterns and smoking trends do not fit a causal hypothesis. Cancers of the Oral Cavity and Pharynx. . . . . . . . . . . page 43 Suspected factors in the workplace, in the environment and in the diet have been statistically related to the development of oral and pharyngeal cancers. Causation has not been determined for these diseases. Cancer of the Pancreas . . . . . . . . . . . . . . . . . . . page 53 Epidemiological research in the U.S. and abroad has suggested many possible risk factors, including smoking, but no specific environmental factor has been consistently associated with the development of cancer of the pancreas. Cancers of the Urinary Tract . . . . . . . . . . . . . . . . page 63 Inconsistencies in mortality trends in bladder and kidney can- cers, associations with diet and occupation and suggestions of other factors requiring investigation leave unanswered ques- tions about reported links with smoking. Cancer of the Lung in Nonsmokers . . . . . . . . . . . . . . page 75 Emotion must not be allowed to obscure the fact that claims linking cigarette smoke to lung cancer in nonsmokers have not been proven. Mortality Data: How Reliable? How Accurate? .......page 91 Extreme caution is warranted in evaluation of epidemiological studies based on mortality data -- such as those used to con- demn smoking -- because errors resulting from clinical misdiagnoses and recording mistakes can affect the accuracy of the mortality data and any conclusions drawn from them. 1

The Board of Editors welcomes suggestions for future editorials that succinctly summarize current work toward a clearly defined hypothesis regarding the causes or cure of cancer. Journal of the National Cancer Institute February 1981 Uncertainty about the causes of cancer is strikingly reflected by the vast amount of public and private funds spent on basic cancer research, the scientific debate on theories of causation and the frequent suggestions that common things in our daily lives might cause cancer. Yet it is not surpris- ing that cancer receives so much attention because it is one of the most serious problems in biology. Unfortunately, solu- tions have not and will not come easily. Only well-conceived and objective scientific research can lead to the resolution of the problem. Despite the recognized limitations in our scientific understanding of cancer, claims often are made that smoking causes the disease. Foremost in the litany of charges against smoking is that it causes lung cancer. In recent years, alle- gations also have included sites ranging from the pancreas and bladder to the kidney and larynx. 1

This document, while not intended to be exhaustive, is an attempt to provide a balanced perspective on some of the issues in the smoking and cancer controversy. The discussions in the following chapters rely on scientific and medical literature to point out why no firm conclusions can be drawn. Unknown Mechanism For Carcinogenesis Even after many years of investigation and millions of research dollars, scientists still are unable to describe the mechanism by which normal cells are transformed into malig- nant, or cancerous, cells. A biomedical scientist noted this fact in the Journal of the National Cancer Institutel in August 1981: A fundamental unsolved problem in the field of cancer biology is the nature of the primary event leading to the production of abnormally proliferating transformed cells. In particular, whether tobacco smoke plays any role in cancer causation is still undetermined. Even a scientist who accepts the conclusion that smoking is causally related to lung cancer wrote in 1979: "Indeed, no mechanism for human tobacco carcinogenesis has yet been successfully formulated and tested."2 2

Animal Studies One of the most common approaches to the study of cancer causation is the exposure of laboratory animals to pos- sible causative agents. Studies of animals exposed to tobacco smoke have produced inconclusive results. Despite considerable efforts scientists essentially have failed to produce in animals the kind of lung cancer most often associated with smoking. In summing up the experimental work in this area, a physician at Yale University said that "no well-designed and well-conducted experiments have shown that cigarette smoke causes lung cancer in animals."3 Epidemiological Studies Advocates of the theory that smoking causes cancer claim substantial support from epidemiological studies. Epi- demiology is a statistical science -- the study of a group of people for both the occurrence of a disease and the detection of factors that might be related to it. Epidemiology deals with statistical relationships and comparisons. It cannot determine cause. As an American Medical Association president once explained, "A statistic is a fact -- the result of a survey -- and that's all it is. Conjectures made on such a statistic are not facts. They are conjectures."4 3

Yet a common mistake made in the interpretation of epidemiological data is the identification of a statistical association as a causal connection. Statistics can never prove a cause and effect relationship; as the AMA official noted, "Statistics pose questions, they don't answer them." What the statistical associations reported in epidemio- logical stu dies can do is su ggest possible leads for further investigation. For example, statistical associations have led to suggestions that diet, place of residence and personality characteristics may be related to cancer. So while epidemiology as a science has its role, it also has serious limitations. The shortcomings of cancer epidemiology in particular were noted emphatically in a state- ment by a prominent biostatistician: "I know of no other scientific activity that's been so naive, so inappropriate, and so unscientific in its lack of attention to the basic data."5 Cancer Rate Patterns The Surgeon General's reports on smoking and health have cited various prospective and retrospective population stu dies to support the claim that a causal link exists between cigarette smoking and cancers of the lung, bladder, kidney, esophagus, larynx, pharynx, pancreas and other sites. Close 4

examination of incidence and mortality rates, however, reveals many patterns that are irreconcilable with the hypothesis that cigarette smoking causes these diseases. Under this hypothesis, disease (or death) rates would be related to smoking patterns or tobacco consumption in a specific way. For example, after tobacco smoking increased (or decreased) in a population, a measurable increase (or decrease) in disease rates would be predicted some years later. This time interval is called the lag period. This refers to the time from first exposure to an agent to the clinical appearance of the disease. Estimates of lag periods published in some scientific papers for smoking and various cancers have ranged from approximately 20 to 40 years. The causal theory cannot, for example, explain the varied patterns in bladder, oral/pharyngeal and esophageal cancer charted in Figure 1.6 Incidence rates of these diseases seem to lack any coherent pattern. They rise, fall or remain stable, depending on disease, gender and race. Even if one considers the so-called lag period, the varied trends still could not be explained by the hypothesis that cigarette smoking is the causal agent. Cancer and the Workplace The view that cancer may be relate d to environmental hazards in the workplace has received increasing attention N U1 0 ~ .~ 4h. N `0 ~ ~ 5

Figure 1 Incidence Rates* per 100,000 Population from Second National Cancer Survey (SNCS) (1947-49) and Third National Cancer Survey (TNCS) (1969-71) SNCS 24 21 -h 18 + 9 -1- 6 -t- 3-h TNCS SNCS TNCS SNCS TNCS 0-' CANCER ORAL CAVITY SITE & PHARYNX 0 0 e I BLADDER ESOPHAGUS Q- white male A - nonwhite male p- white female 0 - nonwhite female N U1 O ~-+ -P ~ N -0 *Age adjusted to the 1950 U.S. population standard v N (6) 6

recently. Research reports suggesting that certain per- centages of cancers are attributable to occupational exposures have stimulated considerable interest in the media. An edi- torial in a recent issue of the Journal of the National Cancer Institute addressed the "need for a systematic approach to environmental carcinogenesis in the workplace." The authors advocated a new epidemiological method to study occupational exposures suspected of increasing the risk of human cancer.7 In some discussions of workplace exposures and cancer, tobacco smoking, alcohol consumption, diet and other lifestyle characteristics are mentioned as possible co-factors. Some investigators have placed the major portion of the blame for the increased risk of cancer reported in some industrial workers on smoking. However, other researchers have expressed concern that focusing on a worker's smoking habit may serve to divert attention away from the hazards of the workplace.8 Mortality Data In order to study the possible relationship between factors, like smoking, and specific disease, researchers generally use information on the causes of death in population groups. Unfortunately, such mortality data often contain errors and inaccuracies. This is especially true in cancer stu dies because of mistakes in diagnosis and record-keeping. W 7

The reliability of death certificates is a major con- cern because they are the main source for mortality data. A group of scientists summarized the problem by saying that death certificates "are sometimes materially inaccurate and research based on them alone may not be secure.°9 A more detailed discussion of the reliability and accuracy of mortality data appears in a subsequent chapter. Conclusion Questions about cancer causation are complex, as demon- strated by divergent theories and the uncertain meaning of research findings. A director of the National Institutes of Health alluded to the problem in a statement to Congresslo a short time ago: In terms of the jig-saw puzzle analogy, medi- cal researchers do not know whether the blue piece they have found is part of the sky, the lake in the background, the evening dress of the girl on the porch or the body of the stationwagon in the driveway. And sometimes they manage to fit it very convincingly into what later turns out to be the wrong place. Independent scientific research, while not always pro- ductive, must continue to be supported in order to close the gaps in current knowledge. In January of 1982, the tobacco industry's research commitment in the smoking and health area 8