Phenobarbital and its Sodium Salt - IARC Monographs on the ...

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<strong>IARC</strong> MONOGRAPHS VOLUME 79
testing. These studies did not include the results for phenobarbital users specifically but
rather for the combined group of barbiturate users.]
In a companion study, based on the 10 368 users of barbiturates, Habel et al.
(1998) observed 34 cases of bladder cancer in the 1992 follow-up, yielding an overall
SIR of 0.71 (95% CI, 0.51–1.0). The SIRs for current smokers <strong>and</strong> former smokers
were 0.56 (0.23–1.2) <strong>and</strong> 0.68 (0.27–1.4), respectively, whereas the SIR for people
who had never smoked was 1.04 (0.48–2.0), indicating an inverse association between
barbiturate treatment <strong>and</strong> bladder cancer risk only among current <strong>and</strong> former smokers.
2.2 Case–control studies (see Table 2)
In order to evaluate the relationships between cancer in children <strong>and</strong> drugs given to
their mothers during pregnancy, S<strong>and</strong>ers <strong>and</strong> Draper (1979) studied 11 169 matched
case–control pairs of children aged up to 15 years included in the Oxford Survey of
Childhood Cancers. A history of epilepsy was reported by 39 case mothers [0.35%] <strong>and</strong>
22 control mothers [0.20%]; a review of available medical records (for 30 case mothers
<strong>and</strong> 18 control mothers) showed no difference in the proportions of mothers in the two
groups who had received phenobarbital (67% <strong>and</strong> 67%). Six of the 39 tumours in
children of mothers with epilepsy were lymphomas, when four cases would have been
expected on the basis of the proportion of lymphomas among childhood cancers in the
population. [The Working Group noted that the number of children with brain tumours
of the 39 mothers with epilepsy was not given.]
In a case–control study by Gold et al. (1978), all children under 20 years of age in
whom brain tumours had been diagnosed in the Baltimore area, Maryl<strong>and</strong> (USA),
between 1965 <strong>and</strong> 1975 were ascertained from multiple data sources, including hospital
tumour registries <strong>and</strong> death certificates. Of a total of 127 children who were eligible for
the study, 84 were included (response rate, 66%) after completion of an interview with
the parents. The parents of 76 population controls [response rate not provided] selected
from birth certificates <strong>and</strong> matched to case children by race, sex <strong>and</strong> date of birth <strong>and</strong>
112 cancer controls [response rate not provided] selected from the same data sources as
the cases <strong>and</strong> matched by race, sex <strong>and</strong> date <strong>and</strong> age at diagnosis were also interviewed
[the items included in the interview were not fully characterized]. These subjects
formed 73 matched pairs of brain tumour patients <strong>and</strong> population controls <strong>and</strong> 78
matched pairs of brain tumour patients <strong>and</strong> cancer controls, which were analysed
separately. In the substudy in which population controls were used, maternal intake of
barbiturates during the index pregnancy was associated with an odds ratio of 2.0 (95%
CI, 0.3–22). Use of barbiturates by the children themselves was associated with an odds
ratio of 2.5 (0.4–26). In the sub-study of matched pairs with cancer controls, the
association with prenatal exposure became significant (lower 95% confidence bound,
1.5). Any use of barbiturates pre- or postnatally was significantly associated with brain
tumours in the analysis with cancer controls (odds ratio, 5.5; 95% CI, 1.2–51), but not
in that with population controls (3.0; 0.8–17). [The Working Group noted that neither