% LaTeX source for Fisher 275 Lung Cancer and Cigarettes




\textit{Nature} \textbf{182} (1958 July 12), 108.

\textsc{The association} observable between the practice of
cigarette-smoking an the incidence of cancer of the lung, to which
attention has been actively, or even vehemently, directed by the Medical
Research Council Statistical Unit, has been interpreted, by that Unit,
almost as though it demonstrated a casuals connection between these

The suggestion\footnote{Fisher, R.\ A., \textit{Brit.\ Med.\ J.}, ii,
43, 297 (1957).}, among others that might be made on the present
evidence, that without any direct causation being involved, both
characteristics might be largely influenced by a common cause, in this
case the individual genotype, was indeed rejected by one
writer\footnote{McCurdy, R.\ N.\ C., \textit{Brit.\ Med.\ J.}, ii, 158
(1957).}, although I believe that no one doubts the importance of the
genotype in predisposing to cancers of all types. 

It seemed to me that although the importance of this factor had been
overlooked by the Unit in question, it was well within the capacity of
human genetics, in its current state, to examine whether the smoking
classes, to which human beings assign themselves, such as non-smokers,
cigarette smokers. pipe smokers, cigar smokers, etc, were in fact
genotypical differentiated, to a demonstrable extent, or whether, on the
contrary, they appeared to be genotypical homogeneous, for only on the
latter view could causation, either of the disease by the influence of
the products of combustion, or of the smoking habit by the subconscious
irritation of the postulated pre-cancerous condition, be confidently
inferred from the association observed. 

The method of inquiry by which such differentiation can be recognized is
the same as that by which the congenital factor has been demonstrated
for several types of disease, namely\footnote{Von Verschuer, F.,
\textit{Proc.\ Roy.\ Soc.}, \textbf{B}, \textbf{128}, 62 (1939).}, the
comparison of the similarities between monozygotic (one-egg) and
dizygotic (two-egg) twins respectively; for any recognizably greater
resemblance of the former may be confidently ascribed to the identity of
the genotypes in these cases. 

I owe to the generous co-operation of Prof.\ F.\ Von Verschuer and of
the Institute of Human Genetics of the University of Munster the results
of an inquiry into the smoking habits of adult male twin pairs on their

The data so far assembled relate to 31 monozygotic and 31 dizygotic
pairs, from Tubingen, Frankfurt and Berlin.  Of the first, 33 pairs are
wholly alike qualitatively, namely, 9 pairs both non-smokers, 22 pairs
both cigarette smokers and 2 pairs both cigar smokers.  Six pairs,
though closely alike, show some differences in the record, as in a pair
of whom one smokes cigars only, whereas the other smokes cigars and
sometimes a pipe.  Twelve pairs, less than one-quarter of the whole,
show distinct differences, such as a cigarette smoker and a non-smoker,
or a cigar smoker and a cigarette smoker. 

By contrast, of the dizygotic pairs only 11 can be classed as wholly
alike, while 16 out of the 31 are distinctly different, this being 51
per cent.\ as against 24 per cent.\ among the monozygotic. 

The data can be rearranged in several ways according to the extent to
which attention is given to minor variations in the smoking habit.  In
all cases, however, the monozygotic twins show closer similarity and
fewer divergences than the dizygotic. 

There can therefore be little doubt that the genotype exercises a
considerable influence on the smoking and on the particular habit of
smoking adopted, and that a study of twins on a comparatively small
scale is competent to demonstrate the rather considerable differences
which must exist between the different groups who classify themselves as
non-smokers, or the different classes of smokers.  Such genotypical
different groups would be expected to differ in cancer incidence; and
their existence helps to explain such oddities as that pipe and cigar
smokers should show much less lung cancer that cigarette smokers, while
among the latter, the practice of inhaling is associated with less,
rather than with more cancer of the lung. 

Dr.\ Bradford Hill, while admitting that the evidence of association
found by his Unit did not amount of proof of causation, has emphasized
that he does not know what else it can be due to.  The facts here
reported do show, however, that the choice is not so narrow as has been
  \textit{Nature} \textbf{182} (1958 July 12), 108.