Tobacco and Public Health - TCSC Indonesia

GRAHAM G. GILES AND PETER BOYLE 491
evidence by some eminent authorities (Anon 1962). The ‘healthy’ cohort effect that gave
rise to the early reduced risks compared with the general population was soon to
disappear as the relative risk between smokers and non-smokers in the cohort increased.
Fisher, on the other hand, emphasized Doll and Hill’s finding from their case–control
study (Doll and Hill 1950), that smokers who developed lung cancer inhaled less often
than smokers who remained free of the disease (Fisher 1958), to suggest that inhalation
was protective against lung cancer. He also pointed to an apparent inconsistency in the
secular trends by sex—that lung cancer rates were increasing more in men than women
while the increase in smoking prevalence had recently been greatest in women (Fisher
1957). He did not comment on the cohort study findings. Because of his scientific
interests, and possibly because of his smoking habit, he was interested in pursuing
studies of genetic susceptibility but these plans were curtailed by his death in 1962.
The paradoxical findings with respect to inhalation patterns were a valid point of
criticism that resisted clarification for some time. It is now known that the deposition
of particulate matter in the bronchi differs by the depth of inhalation, deep inhalers
depositing less in the bronchi and more particulates deep in the lungs (Wald et al. 1983).
The concern about trends by gender was misplaced, as it failed to take into account the
long latency period between exposure and the diagnosis of lung cancer and the strong
cohort effects in the uptake of the smoking habit that differed between the sexes.
The consistency of the association
The consistency of the findings shown by the early case–control and cohort studies has
been maintained in numerous additional studies since that time that have been conducted
in many different populations (IARC 1986). The consistency of the evidence
from these analytical studies has been reinforced further by ecological studies of lung
cancer trends in populations that have shown a high correlation between smoking
rates and lung cancer rates both within populations and internationally (Doll 1954;
Doll and Peto 1981). Analysis of lung cancer mortality trends over time have shown
pronounced cohort effects associated with the prevalence of smoking (USDHHS
1982), and in some populations where male smoking prevalence has fallen, so too is
lung cancer mortality (Gilliland and Samet 1994).
The strength of the association
Strength of association is perhaps the single most important criterion in establishing
causation. It is usually expressed as the ratio of the incidence of disease in those
exposed to the causal agent (in this case smoking) to the incidence of the disease in the
unexposed. In cohort studies this ratio is termed the relative risk, which is approximated
in case–control studies by the odds ratio. In cohort studies, the estimates of relative risk
of lung cancer comparing cigarette smokers with non-smokers range from 9 to 14-fold
(Doll and Hill 1954; Hammond and Horn 1954; Hammond 1966; Cederlof et al. 1975;
Doll and Peto 1976; Lund and Zeiner-Henriksen 1981).