University of Oxford, Nuffield Department of Medicine, CTSU, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, UK.
The issue of Zeitschuft für Krebsforschung in which Schairer and Schöniger's1 paper appeared did not reach Britain during the war (although most other issues did) and it is still not held by many libraries and was not indexed in the cumulative medical index. It is understandable, therefore, that it was not mentioned at the conference held by the Medical Research Council in 1947 to discuss the reasons for the increase in mortality attributed to lung cancer (Hill, personal communication) and was not referred to when Hill and I published our first paper on the association between cigarette smoking and lung cancer,2 although we did refer to Müller's paper that had been published in 1939.3 Schairer and Schöniger's paper came to the attention of British research workers sometime in the next 2 years and was listed as one among several papers that had previously reported an association between smoking and lung cancer in the final report of our case-control study4 and it was subsequently noted regularly in reviews of the subject on both sides of the Atlantic. In Germany it received a mixed reception. It was mentioned by Bauer5 in his textbook on cancer (though its conclusions were not endorsed) and was accepted in East Germany by Lickint6 who had long been convinced of the hazards of smoking. In West Germany, however, interest in the effects of smoking waned, as a reaction to the anti-smoking policies of the Nazi government, and it came to be ignored. It has consequently never been properly reviewed and its conclusions not emphasized until Davey Smith, Ströbele and Egger drew attention to it 50 years later in an article on Nazi medicine in the Journal of Epidemiology and Community Health in 1994.7
Judged by modern standards of epidemiology Schairer and Schöniger's work fails on several grounds: (1) the small number of cases of lung cancer (93 men and 16 women), (2) the use of surrogate informants for the patients who had died from cancer and living informants for information about themselves for the controls, (3) the low response rate to the questionnaires about the cancer patients (53% for those with lung cancer, 4060% for those with cancers of the tongue, oesophagus, stomach, colon, and prostate, and an even lower rate [39%] for the controls) and (4) the use of controls in only one narrow age group (5354 years) selected to correspond with the average age of the lung cancer patients (53.9 years).
The epidemiology of non-communicable diseases was, however, in its infancy at the time and it would be unfair to the authors to judge their work in this way. However, it should be noted that much higher standards had already been set in a few studies, notably in the UK by Lane-Claypon8 in her study of 500 cases of breast cancer and 500 controls and by Stocks and Karn9 in their study of the diet of 462 patients with a variety of cancers and 435 controls, and in the US by English et al.10 in their study of smoking and myocardial infarction.
The strength of Schairer and Schöniger's study lay in the fact that they compared their findings for people who had died from lung cancer with those for people who had died from other types of cancer, principally stomach cancer (then the most prevalent type of fatal cancer in Germany, as it was in most of the developed world), as well as with their findings for healthy controls. Its value lies principally in their percipient discussion of the meaning of their findings.
They noted the great differences they recorded in the proportions of heavy smokers and of non-smokers in their lung cancer patients compared with those recorded for gastric cancer and control subjects and the similarity of their results with those obtained earlier by Müller3 (whose findings had stimulated their enquiry). They also highlighted the increase in the frequency with which lung cancer had occurred over the previous 20 years, its correspondence with the increased use of tobacco, the greater frequency of the disease in men than in women (corresponding to the sex difference in smoking), the successful induction of cancer on the skin of animals by the application of tobacco tar by Roffo11 and the presence in such tar of the strongly carcinogenic benzpyrene. When all these pieces of evidence were combined Schairer and Schöniger thought the total evidence made a strong case for causality, particularly as they were able to cite several reasons (q.v.) for thinking that occupation, combustion engines and city life could not account for the findings. Their list of evidence, it may be noted, includes most of the types described later by Hill12 as guidelines that could be used to determine causality.
One piece of the evidence would, however, have been disputed in the UK, for the temperature at which Roffo burnt his tobacco was greater than the temperature at which tobacco is burnt in normal smoking and, although Kennaway's colleagues eventually showed that benzo(a)pyrene was present in normal tobacco smoke in small amounts13 and Wynder et al.14 showed that cancers could be produced on the skin of animals by prolonged painting with tars produced at the appropriate temperature, Roffo's experiments should not have been cited as biological evidence of the plausibility of a causal relationship.
Schairer and Schöniger realized the weaknesses in their study and noted that the proportion of non-smokers in their comparison groups were suspiciously high and that the low response rate in the controls might have biased the results; heavy smokers in particular having refrained from replying. Although these considerations should not, they thought, have applied to the other cancer comparison groups. Stomach cancer patients, however, might have suffered from a weak stomach for some time and consequently refrained from heavy smoking. They recognized that their comparison material was less than satisfactory and reached the cautious conclusion that the association between heavy tobacco consumption and lung cancer is therefore statistically, and causally, only likely and that larger investigations are required.
Schairer and Schöniger's article marks an important phase in the development of knowledge about the harmful effects of tobacco and has, until now, failed to receive the recognition that it deserves. It would be wrong, however, to suggest that it proved, beyond reasonable doubt, that smoking was an important cause of the disease, a conclusion that the authors themselves never claimed.
References
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2 Doll R, Hill AB. Smoking and carcinoma of the lung. Preliminary report. BMJ 1950;2:73948.
3 Müller FH. Tabakmissbrauch und lungencarcinoma. Z Krebsforsch 1939;49:5785.
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5 Bauer KH. Das Krebsproblem. Berlin: Springer-Verlag, 1949.
6 Lickint F. Ätiologie und Prophylaxe des Lungenkrebses. 2. Statistische Voraussetzungen zur Klärung der Tabakrauchätiologie des Lungenkrebses. Leipzig: Theodor Steinkopff, 1953, pp.76102.
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