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3. Other substances
Substances other than organochlorine pesticides were addressed
only by Aschengra et al. (1998) in a population-based
case-control study, in which alkylphenols and bisphenol A did
not show significant risk increase. Increased variety of
exogenous estrogens did not raise the risk either. The exposure
history of the subjects was estimated by their occupational
experiences in ths study.
[Discussion]
Recent cohort studies recognize unanimously that DES slightly
increases breast cancer risk. Although the relationship of the
risk with DES exposure level is not fully determined, it is
plausible to say that practical doses as prescribed for internal
use increases the risk by about 30%. It is not established,
however, that longer periods since the exposure increases the
risk.
Case-control reports on organochlorine compounds are amply
reported, of which hospital-based studies represented the
majority. However, any increase in the risk was observed by
about the half of the reports, and they disagree about which
substance is significantly affecting. Also, these hospital-based
studies is not uniform in quality: the number of reports cannot
be the ground for decision about the risk. The more reliable
nested cohort studies found risk increase by dieldrin, some PCB
homologues and HCB, but the specific results do not agree with
each other. The risk increase by organochlorine compounds are so
small, if any, that it may readily be hidden by a bias. Laden et
al. (2002) analyzed the pooled results of five case-control
studies (2 nested, 3 retrospective) in North America to find no
significant risk. A meta-analysis by Lopez-Cervantes et al.
(2004) of the results of 22 studies on p,p'-DDE (9 nested
case-control, 5 population-based, 7 hospita-based of which 1
using a control population) did not find significant risk
increase, either. On the other hand, stratification according to
the polymorphism of metabolic enzyme genes revealed significant
risk in a study. Saintot et al. (2004) suggests in a case study
that women who have CYP1B1 Val allele are susceptible to breast
cancer risk increased by exposure to organochlorine compounds in
the environment (farm work or waste treatment plant near homes).
Future studies will need to take in to account interactions
between the genetic system and the environment. At present, it
is impossible to conclude that organochlorine compounds increase
breast cancer risk.
Only one report addressed chemical substances other than DES and
organochlorine compounds. No study used serum concentration or
other biomarkers.
While epidemiologic studies on the correlation of breast cancer
with DES and organochlorine compounds are fairly numerous as
described so far, other substances have hardly been
investigated; it was impossible to estimate the causality.
Future studies must be extended to include those substances. No
report included studies on Japanese subjects. Considering
genetic and environmental differences, e.g. diet containing more
isoflavones that seems to reduce breast cancer incidence,
studies on Japanese subjects should be promoted.
[Conclusions]
Review of epidemiologic studies on the relationship of chemical
substances with breast cancer did not provide a clear evidence
that organochlorine compounds increase the risk. DES is reported
to increase breast cancer risk in more than one study. Effects
of substances other than DES and organochlorine compounds are
hardly studied and the causal relationship between the
substances and breast cancer cannot be estimated adequately.
Experimental designs with high reliability are needed for future
studies on this problem.
[Literature]
Table 2.1.1: Cohort studies on the relationship of endocrine disruptors with breast cancer
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