Francine Laden et al., Journal of the National Cancer Institute 93(10):768-776
and polychlorinated biphenyls and breast cancer: combined analysis of
five U.S. studies.
It is widely recognized
that the incidence of breast cancer has been increasing over the past
50 years. However, the cause for this rise in breast cancer rates remains
an enigma. It has been suggested that exposure to hormonally active
agents (HAAs) in the environment may play a significant role. Consequently,
the relationship between organochlorine exposure and breast cancer risk
has been studied extensively. In particular, the association between
exposure to organochlorine chemicals such as polychlorinated biphenyls
(PCBs) and the major in vivo DDT metabolite, 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene
(DDE), persistent synthetic environmental toxicants that accumulate
in body tissues, and breast cancer has been examined. The present study
is important because it represents a combined analysis of five large
U.S. studies that evaluated the association between breast cancer risk
and organochlorine exposure. The studies were Western New York, Mount
Sinai, Yale, Campaign Against Cancer and Stroke (CLUE I), and the Nurses'
Health Study (NHS). All five studies concluded that there was no association
overall; however, specific subgroup effects were observed. The authors
of the present study reanalyzed the data by using a standardized approach
to control for confounding factors and to assess effect modification.
The five studies included population-based and hospital-based case-control
and nested case-control designs. In total, the studies comprised 1400
breast cancer patients and 1642 control subjects and the majority of
the participants were postmenopausal. The combined evidence reported
in this study does not support the hypothesis that elevated plasma or
serum concentrations of PCB and DDE increases the risk of breast cancer.
However, limitations do exist in combining studies with different designs.
Yale analyzed the lipid-adjusted levels of PCB and DDE using a gravimetric
determination whereas the other studies calculated total lipids from
total cholesterol and triglycerides. These methods may yield different
values. In addition, time of blood collection and location of participant
residence differed between studies and may have influenced the observed
absolute values. Furthermore, plasma and serum measurements were taken
more than 10 years after the ban of these chemicals in the United States.
Because of the long half-lives of these compounds, the observed levels
were predicted to be indicative of past exposures. Although PCB and
DDE are the most persistent and most easily detectable organochlorines,
they are not necessarily the most toxic. Also, PCB congener concentrations
in breast tissue are only weakly correlated with levels in blood; reliance
on blood indices alone would substantially misclassify women's exposures
at the tissue level, likely causing an underestimation of any association
between PCBs and breast cancer. The present study does not rule out
the possibility that these toxicants or other hormonally active agents
in the environment may be associated with breast cancer risk.