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PETO .ral history of COLD ends for lung cancer, aere are other impor- ,t a time when there i fferent social classes cause of death in the women. Since then, :ddle-aged men have all. It is very difficult cannot confidently ution decreases pro- e correct one. directly informative nposition on COLD . even less informa- ~e, they might even ight be to study the :ond Forced Expira- ~re the FEV had got ecent such study has • an individual basis, ;e~et rates (i.e. in • ~I~Y case, even if smoke were chiefly ways of producing ,moke components) ~tte modification to aas been introduced cigarette by a small gation of the physi- y lead to the design • to kill about 20 or .ment of their use is be quite different), re attention than it TOBACCO-RELATED DISEASE 135 A variety of WHO and UICC expert reports have been prepared on how voluntary organizations and governments can decrease cigarette consumption, and these deserve careful scrutiny, for they contain much well-judged advice. There are, however, two important respects in which they may be somewhat deficient. The first is that tax increases are not sufficiently emphasized. Because many governments derive large tax yields from tobacco sales, all the strategies that may be considered for reducing cigarette sales will also, if effective, reduce tax revenues, except for an increase in the taxation of tobacco. Although in principle governments may believe they act only for the good of their citizens, in practice they may tend to decide that what is economically easiest for the government is best for the citizens. Consequently, the one strategy--increasing the tax on tobacco---that increases rather than decreases tax revenues, even when sales are decreased, perhaps deserves more emphasis than it usually gets, especially because it is one of the few strategies for which there is clear, direct evidence of effect. A second deficiency of emphasis is that there may have been insufficient stress on the long-term advantages of getting quantitatively informative mater- ial across about the total risks from tobacco, and the extent to which, at least in developed countries, these exceed all other reliably known causes of death. It is admittedly difficult to communicate risks in a way that will be understood and remembered approximately correctly, especially by people who have no framework of other risks with which to compare them. However, this should be possible, so long as the main message is set clearly apart from the lesser mes- sages that qualify it. After all, the chief message is merely that 'ABOUT A QUARTER OF ALL REGULAR CIGARETTE SMOKERS WILL BE KILLED BEFORE THEIR TIME BY THE HABIT', which is considerably less complicated than the mass of quantitative information about house prices, groceries, car prices, etc. that already has become part of the folklore of consumer societies. How exactly this main message should be put over is a matter for experiment: comparisons with other conditions may (especially in Britain) be helpful, for example: SMOKING IS BRITAIN'S BIGGEST KILLER Among 1000 young adults who smoke cigarettes regularly, --about 1 will be murdered --about 6 will be killed on the roads --about 250 will be killed by tobacco. Even in the United States, where road accident death rates are more than double those in Britain and murder rates are about ten times those in Britain, some such comparisons may be helpful (although it may then be advisable to start with only 100 young United States adults, and to threaten about 1, 2 and 25 of them with death). Whatever format is preferred, however, the central point remains: the

I I|111111111111 II II II III IIIIIIIII III 136 PETO reason one wants to prevent smoking is not just because it is danger- ous--dozens of things are dangerous--but because it is so dangerous. This indicates getting some sort of quantitative information over, both about the effects of smoking itself on mortality and, perhaps at least as importantly, about how much smaller all reliably known other carcinogenic effects are. Such in- formation may in the short term make only a few people give up, but over a few years wide acceptance of such a perspective may have substantial effects, either on individual behaviour or on making other actions political!y acceptable. CONCLUSION Large changes in cigarette usage can be produced by socially acceptable means (Table 2). In Britain, for example, cigarette usage per adult has decreased by about 30% over the past decade alone, Likewise, tar level reductions can fairly easily be implemented, especially in countries such as Russia and China where cigarettes are manufactured and distributed by the State with little advertising and where typical tar deliveries exceed the upper limit of what is currently sold in Britain. TABLE 2 Information for governments on simple measures for the control of lung cancera Price increases will produce fewer deaths and more revenue (as long as the)' do not feed back into wage demands) Tar reductions should be encouraged (especially in countries such as Russia and China where typical tar levels are still of the order of 20-30 mg, which is extremely high) Advertising could be taxed, restricted, prohibited, or limited to cigarettes delivering under I0 mg tar Simple, clear, quantitative information could be communicated effectively ~o the general population: ABOUT A QUARTER OF ALL REGULAR SMOKERS ARE KILLED BEFORE THEIR TIME BY TOBACCO I General note: recommendation of these few simple measures (which might have a substantial effect in just a few years on exposure) does not, of course, detract from the need for a wide range of other measures, including many of those suggested by WHO (1979), UICC (Gray 1977), and others. Modificztions of the consumption and of the composition of cigarettes are complementary, not competing, strategies that together could lead to avoidance of most of the 100 000 or more tobacco-induced deaths each year in Britain, most of the 300000 or more in the US, and some hundreds of thousands in the rest of the world. Such changes will, perhaps surprisingly, TOBACCO-REL not greatly cha developed cou~ in middle age. REFERENCE~ Cederl6f R. Doll assessment meth Doll R. Peto R It. doctors. Br Med Doll R. Peto R 19~ United States to,_ Gray N (ed) 1977 1. Contre le Cancer Independent Scien Stationery Offic~ Kaufman DW. He monoxide conter 308:409-413 Lee PN 1976 Stat~ Research Counc~ Lee PN, Garfinket 35:16-22 Peto R. Speizer FE Richards SM. Gi but not of mucus 128:491-500 Wald N, Idle M, B cigarette. Thorax Winn DM, Blot cancer among w~ World Health Org~ committee on sm DISCUSSION Doll: I don't ' disease in Brita diagnostic habit 20 or 30 years a~ term. The diff, differences, bec Koplan: You obstructive lung

PETO ~cause it is danger- ~ so dangerous. This ~ver, both about the as importantly, about effects are. Such in- ve up, but over a few tantial effects, either =ally acceptable. tlly acceptable means lult has decreased by reductions can fairly sin and China where ,'ith little advertising .'hat is currently sold I of lung cancer~ ~ot feed back into ~ussia and China where s delivering under 10 mg ectively to the general LED BEFORE THEIR night have a substantial need for a wide range of .~ICC (Gray 1977), and 9n of cigarettes are ~er could lead to deaths each year in some hundreds of rhaps surprisingly, TOBACCO-RELATED DISEASE 137 not greatly change the life expectancy of old people, but they will, at least in developed countries, appreciably decrease the proportion of people who die in middle age. REFERENCES Cederlrf R. Doll R. Fowler B, Friberg L, Nelson N, Vouk V 1978 Air pollution and cancer: risk assessment methodology and epidemiological evidence. Environ Health Perspect 22:1-12 Doll R. Peto R 1976 Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J 2:1525-1536 Doll R, Peto R 1981 The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66:1191-1309 Gray N (ed) 1977 Lung cancer prevention: guidelines for smoking control. Union Internationale Contre le Cancer, Geneva Independent Scientific Committee on Smoking & Health 1983 Third Report. Her Majesty's Stationer3' Office. London Kaufman DW. Helmrich SP, Rosenberg L, Miettinen OS, Shapiro S 1983 Nicotine and carbon monoxide content of smoke and the risk of myocardial infarction in young men. N Engl J Meal 308:409-413 Lee PN 1976 Statistics of smoking in the United Kingdom. Research Paper No. 1. Tobacco Research Council, London Lee PN, Garfinkel L 1981 Mortality and type of cigarette smoked. J Epidemiol Community Health 35:16-22 ~ Peto R, Speizer FE, Cochrane AL, Moore F, Fletcher CM, Tinker CM, Higgins ITr, Gray RG, Richards SM, Gilliland J, Norman-Smith B 1983 The relevance in adults of airflow obstruction. but not of mucus hypersecretion, to mortality from chronic tung disease. Am Rev Respir Dis 128:491-500 Wald N, Idle M, Boreham J, Bailey A 1980 Inhaling habits among smokers of different types of cigarette. Thorax 35:925-928 Winn DM, Blot WJ. Shy CM. Pickle LM, Toledo A, Fraumeni J 1981 Snuff-dipping and oral cancer among women in the Southern United States. N Engt J Med 304:745-749 World Health Organization 1979 Controlling the smoking epidemic: report of the WHO expert committee on smoking control. Technical Report Series 636. WHO, Geneva DISCUSSION Doll: I don't think one can really compare trends in chronic obstructive lung disease in Britain and the US. There were formerly enormous differences in diagnostic habits between the two countries, which have diminished in the last 20 or 30 years as a result of physicians getting together and deciding to use this term. The differences in trends can be largely attributable to nosological differences, because the national statistics have started from a different base. Koplan: You say that there are other aetiological factors involved in chronic obstructive lung disease (COLD), in addition to smoking. In lung cancer itself,

138 DISCUSSION you suggest that one means of comparing low tar cigarette smokers to high tar sm6kers is to compare data over time. Tar content clearly is the major compo- nent in lung cancer, but are there likely to be other aetiological agents for lung cancer as well, in parallel to COLD? Peto: There certainly are other host factors in lung cancer. There are obvious ones, like asbestos and ionizing radiation. It is also possible that there are nutritional components in lung cancer, or that infective processes could be relevant. I don't think changes in air pollution can be plausibly invoked as causes of the changes over time. partly because air pollution was never an important cause of lung cancer anyway, and partly because one sees the same trends in Finland, a country that has never been seriously polluted (outside the sauna baths!). Blanpain: The pine woods in Finland produce substantial air pollution: substances such as turpentine are turned into carcinogenic smog under the influence of sunlight. Peto: Changes in air pollution from pine forests are not responsible for the 40% decrease seen in Finnish lung cancer rates between the early 1960s and the late 1970s. The number of cigarettes per man smoked in Finland, like that in Britain, stayed roughly constant until the mid 1970s and only then began to fall, with large price increases. The tar deliveries fell enormously, because there was a switch from Russian-type cigarettes to modern Western low tar cigarettes. In fact, the fall in tar delivery in Finland was greater than anywhere else in the world, and we saw a 40% decrease in lung cancer incidence in early middle age by the late 1970s. By now, the decrease may be beyond 50%, as it is in Britain. Miteva-Toncheva: We are confronted here with a very complex problem, namely the interaction between environmental factors and the individual's genotype (for example, the effects of tobacco on potentially susceptible indi- viduals). Have you investigated al-antitrypsin variants by isoelectrofocusing? Homozygotes for deficiency of this protease inhibitor, and heterozygous car- riers, are highly susceptible to chronic obstructive lung disease (COLD) under the influence of tobacco. Such individuals form a high risk group, and it is very important to give more care to them. Peto: For homozygotes, that is true. People deficient in this inhibitor finish up with proteases coming out of their alveoli, so wrecking their lungs complete- ly, and may die of COLD at the age of 40. Homozygotes with al-antitrypsin deficiency are rare and are at enormous risk of this lung disease, if they smoke. Heterozygotes are an appreciable proportion of the population and some studies have suggested that they are at increased risk but, overall, there seems to be no substantial difference in risk between heterozygotes and people of normal genotype. But there must be genetic deter)ninants of the response to cigarette smoke of the heart, lungs, and other systems. However, we can change the environment, but we can't change the genotype. TOBA Met smoki peopl~ ischae decre: Pet, could variot, On smoki and ht switch cigare moutl- don't becau their i~ that ci manta in the chang~ Hje., (CHD becau, the 0, sclero, reasor Pet~ CHD so extz from .~ fivefol high a Sec~ extren diseas, causal Dan smokil only c, (Fribe" young, 0

DISCUSSION okers to high tar ~e major compo- agents for lung here are obvious e that there are ,cesses could be ~ibly invoked as n was never an ~e sees the same ~ted (outside the air pollution: ~mog under the responsible for early 1960s and and, like that in _~n began to fall, cause there was ir~rettes. In ~glse in the arI~middle age it is in Britain. ~plex problem, he individual's ~sceptible indi- ectrofocusing? erozygous car- COLD) under ~, and it is very nhibitor finish tngs complete- al-antitrypsin if they smoke. on and some 1, there seems md people of e response to ever, we can TOBACCO-RELATED DISEASE 139 Meade: What is the current status of the evidence on cigars in relation to smoking-related disease, cardiovascular or malignant, now that so many more people are smoking them? You also mentioned the high relative risk of ischaemic heart disease in younger cigarette smokers, and the fact that it decreases with increasing age. Have you any ideas why that is? Peto: I don't know why the relative risk changeswith age like that. You could produce models in which you eliminate susceptible sub-groups in various ways, but that is a mathematical exercise, not a biological one. On the question of cigars, one has to distinguish between two types of cigar smoking. The first is in people who smoked cigars when they began smoking and have smoked them throughout their lives. There are also people who have switched from cigarettes to cigars because they want to avoid the health risks of cigarettes. Long-term cigar smoking confers a certain risk of cancer of the mouth and throat, but nothing like the lung cancer risk of cigarettes. But we don't know what will happen when people switch from cigarettes to cigars, because this could produce quite different effects. These people may carry over their inhaling patterns to cigars. There is not much evidence, in animals at least, that cigar smoke is less hazardous than cigarette smoke. It is perhaps chiefly the manner in which the cigar is smoked that is protective, rather than differences in the make-up of the smoke, except insofar as these differences produce changes in the manner of smoking. Hjermann: I believe that smoking is causally linked to coronary heart disease (CHD), but I am not quite sure how firmly I should believe this! It is partly because of the lack of controlled trials in this field. In a prospective study like the Oslo trial, we could not find any significant correlation between athero- sclerosis and smoking. It seems to be hard to show. What are your main reasons for believing in this causal relationship? Peto: The fundamental reason for believing that the relationship between CHD and smoking is a causal one is that the relative risk in early middle age is so extreme. Among people in their thirties, CHD is rare but the relative risk from smoking is as much as 10-fold. In the 40-44 age group there is still a fivefold relative risk. So the relative risk between the ages of 30 and 50 is so high as to make non-causal explanations rather implausible. Second, peripheral vascular disease and aortic aneurysm have even more extreme relative risks among smol~ers than CHD does. For peripheral vascular disease the association is so extreme as v~,rtually to preclude anything except a causal explanation. Danielsson: There is still some question about the causal correlation between smoking and ischaemic heart disease, in my view. A twin study showed that the only certain correlation between smoking and disease was for lung cancer (Friberg et al 1973). The problem with evidence for causality dra~vn from the younger smokers is that you don't have a good control group. We should always

-- - IlII lilllllll ..... I III , ............. ,, ,,,, , ........... 140 DISCUSSION TOBACCO-F bear in mind that perhaps a smoker is different from a non-smoker; that is, smokers may be more prone to this disease, whether or not they actually smoke. This is why it is so difficult to do a conclusive study. Peto: This is not a plausible hypothesis where the relative risks are so extreme. The twin studies are much overrated, Like randomized trials, they would be fine if done on a scale one or two orders of magnitude bigger than they • .are done. When the evidence from homozygous and heterozygous twins is studied, and one looks at the actual numbers of events and how much differ- ence there was in smoking, there is not enough evidence to add usefully to that from much larger studies. Hiatt: Is any effect on cancers other than those in the respiratory tract visible yet, with the changes in cigarette smoking? And what are your present thoughts about interactions between cigarettes and other carcinogens? Peto: We can't really assess the effects of changes in cigarette composition on say, cancer of the bladder, although Paolo Vineis has suggested, on the basis of his large but unpublished case-control study, that black tobacco (like that in Gauloises, for example) is peculiarly hazardous. One would probably learn more by measuring the extent to which the urine of smokers is mutagenic when they are smoking different types of cigarette, taking the mutagenicity of the urine as a surrogate for epidemiology. Some types of cigarettes deposit sub- stantial amounts of benzidine into the bladder. The chief source of benzidine that people are now exposed to in Britain is from cigarettes, rather than the industrial use of dyes and other chemicals. Doll: Mortality from cancer of the bladder and of the pancreas---diseases that are not very strongly related to tobacco use--is either falling or static in the UK. However, the incidence rates of some cancers that are closely related to tobacco--cancer of the mouth, oesophagus and larynx--are going up. These last changes presumably result from the increase in alcohol consumption, which is even more strongly related to these cancers. These changes illustrate the complexity of drawing conclusions about the effect of specific aetiological agents from mass statistics. If I wanted to argue that cigarette smoking was not proved to be the cause of any type of cancer, I would point to the trends in cancer of the larynx in various countries. Although this cancer has been closely related to cigarette smoking in all case-control studies, the trends in incidence and mortality have sometimes been in the opposite direction to the trends for cancer of the lung. To my mind, the only reasonable explanation is that other factors of which we are still ignorant account for these exceptions. But if you want to allow an exception to disprove a massive set of evidence, you point to the trends in cancer of the larynx. These cases are important to investigate because they are exceptions, but we ought to beware of allowing such exceptions to undermine a mass of contrary evidence, when we ar and the pro. Shephara naive to thi into sugges other risks will make i With reg obtained bx In fact, wit cigarettes, Peto: Th airways. I a the alveo/i reductions, young peoI continue t~ tendency tt levels--the levels were when Japm took up th~ that high t~ Koplan: cigarette s~ non-tobacc Peto: I d, between cc The comm public pres really seri~ European efforts; it c health, or problem s~ where the serious, an reduction, years, whi, Eddy: V~ of tobacco

DISCUSSION • moker; that is, ~t they actually ve risks are so zed trials, they qgger than they zygous twins is ,w much differ- usefully to that ory tract visible ,resent thoughts composition on • on the basis of co (like that in probably learn ~utagenic when genicity of the es deposit sub- ze of benzidine ,, or static in the ~sely related to ~ing up. These consumption, ions about the anted to argue pe of cancer, I ries. Although 11 case-control .~s been in the mind, the only • still ignorant on to disprove • larynx. These ,ut we ought to rary evidence, TOBACCO-RELATED DISEASE 141 when we are trying to interpret the relationship between aetiological agents and the production of disease. Shephard: You discussed the tactic of emphasizing tar reduction. It may be naive to think that cigarette manufacturers are not going to pervert this view into suggestions that we believe low tar cigarettes to be safe. There may be other risks with this tactic, one being that the lower levels of tar and nicotine will make it easier for young people to become addicted to cigarettes. With regard to the figures for the tar content of cigarettes, these are all obtained by smoking machines which presuppose a certain pattern of smoking. In fact, with the change in pattern of smoking that one gets with low tar cigarettes, there may be very little reduction in the tar delivered by them. Peto: There may be a substantial difference in tar delivery to the main airways. I agree that there may be no great change in the amount that reaches the alveoli. However, in countries where there have been good tar level reductions, there have also been considerable reductions in the extent to which young people are taking up smoking and also in the extent to which adults continue to smoke. That is not always true. but at least there is no systematic tendency the other way. Conversely, consider countries with very high tar levels--the USSR at present, or Japan in the 1950s. At that time in Japan, tar levels were high. Smoking by minors was forbidden during those years, but when Japanese males reached adulthood, about 80% of the male population took up the smoking of high tar cigarettes. So there is no suggestion, either, that high tar levels discourage people from starting to smoke. Koplan: Are there any differences in the level or type of effort to curtail cigarette smoking among countries that are tobacco producers, as against non-tobacco producers? Peto: I don't really know. There does, however, appear to be a big difference between countries where tobacco manufacture is in private and in public hands. The communist countries have been terrible; I suppose there is no effective public pressure on those governments to act, and so they have done nothing really serious to discourage smoking in the USSR, China or any Eastern European country. In at least some Western countries there have been serious efforts; it depends very much on concerned individuals within departments of health, or within the population generally. One or two people who take the problem seriously can make a vast difference to a whole country. In France, where the State manufactures tobacco, the government has done nothing serious, and in Britain it has. Perhaps partly because of this, Britain has seen a reduction of one-third in the number of cigarettes smoked over the last i0 years, which is a considerable success that should be emulated elsewhere. Eddy: What role do you think nicotine chewing gum might play in the control of tobacco-related diseases?

142 DISCUSSION Peto: A relatively minor one. Various randomized trials have suggested some effect, though not a large one. But, because the problem is so important, a minor effect on a major disease represents a useful public health advance, so it is a worthwhile aid that should be introdu_ced, encouraged and used. Any- thing that helps to get people off cigarettes is a good idea. We have to find out what works for different people, and nicotine chewing gum helps a few people. REFERENCE Friberg L, Cederl6f R, Lodch U et al 1973 Mortality in twins in relation to smoking habits and alcohol problems. Arch Environ Health 27:294-304 Screenir related Malm6 " BO PETERSSOt' Section of Preve: S-214 O1 MalmO, Abstract. related di: in a large underlyin! In a pr~ death in n most pred cant corre tively, ant In the r admissior group, af" prcventir related di as the ret high/non 1985 The p 143-16 The preventi broad progrz as individual complete eli~ Three mai phasized, na subject, and The purp~ individual st.