M, B Eskenazi, P Mocarelli, PM Gerthoux, S Samuels and L Needham.
2002. Serum Dioxin Concentrations and Breast Cancer Risk
in the Seveso Women’s Health Study. Environmental
work in the aftermath of the 1976 Seveso, Italy, pesticide factory
accident failed to establish links between dioxin exposure and breast
cancer incidence. This new study of Seveso residents by Warner et
al. finds that breast cancer risk increases significantly
with higher dioxin exposures. The authors suggest that
an earlier study, covering only the first decade after the accident,
had not allowed sufficient time to pass since exposure for dioxin's
impacts to be manifest.
findings highlight the reality that the consequences of exposure
may not be manifest for decades, and that to understand
the causes of breast cancer you must know about chemical exposures
years before diagnosis. This study reinforces the argument
that epidemiological work examining contamination levels at the
time of diagnosis (for example, the
Long Island Breast Cancer Study) are of limited value for establishing
(or refuting) the causes of breast cancer.
did they do? Warner et al. measured dioxin (specifically
2,3,7,8-tetrachlorodibenzo-p- dioxin, or TCDD) levels in
blood samples that had been taken shortly after the accident and
stored. They used data from the Seveso Women’s Health Study
(SWHS), "a historical cohort study of the female population
residing around Seveso at the time of the explosion in 1976."
"Women eligible for the SWHS were infants to 40 years old in
1976, had resided in one of the most highly contaminated zones,
A or B, and had adequate stored sera collected soon after the explosion."
used health records to identify women within the cohort who had
developed breast cancer by mid-1998 and then performed a series
of statistical analyses comparing dioxin levels in women with vs.
those without a cancer diagnosis. Their analysis included extensive
work to control for the effects of factors known to affect the risk
of breast cancer, including: age at first pregnancy, age at last
pregnancy, lactation, family history of breast cancer, age at menarche,
smoking, and alcohol consumption, etc.
did they find? Warner et al. identified 981 women
in the SWHS cohort who met the criteria of the study. Of them, 232,
279, 241 and 229 were 0-10, 11-20, 21-30 and 31-40 years old, respectively,
at the time of the explosion. Among them, 15 women had been diagnosed
with breast cancer (1.5%).
average age of women at the time of the explosion who by 2001 had
been diagnosed with breast cancer was 30.1 years (ranging from 14-39
years). Their average age at the time of diagnosis was 45.2 years.
The average timelag between the explosion and breast cancer diagnosis
was 15.2 years (range 8-21 years).
et al. found that a 10-fold increase in dioxin
levels was associated with a 2.1 increase in risk for breast cancer.
Despite the small number of cases, the increase was statistically
et al. acknowledge that the small number of breast cancer
cases in their cohort limits the strength of their conclusions.
does it mean? This paper reinforces previous other studies
finding statistical links between dioxin exposure and breast cancer
risk, for example, women
working in contaminated chemical plants. And because of the
stored blood samples and the increasing duration of the study (i.e.,
length of time over which the effects of exposure might be manifest),
Warner et al. had significant advantages over other studies.
advantage of the SWHS is that we were able to examine the
relationship between serum TCDD concentration and breast cancer
incidence, thus eliminating potential bias associated with
disease survival. In addition, we were able to collect information
during the interview, allowing consideration of potential
confounding by known risk factors in the analysis. Finally,
we were able to measure individual serum TCDD concentrations
near the time of exposure, thus minimizing exposure misclassification."
et al. discuss two other studies of breast cancer in Seveso-exposed
first reported no link to dioxin exposure. This work, published
in 1993, covered breast cancer cases diagnosed through to 1986,
i.e., one decade after the explosion. As Warner et
al. observe, 13 of the 15 breast cancer cases in their cohort
were diagnosed after 1986.
second reported an apparent increase in breast cancer risk
with rising dioxin exposure but found it to be insignificant.
et al. comment that the women in the SWHS cohort are only
now, on average, entering the age of maximum risk to breast cancer.
cancer incidence increases steadily with age, with the most
rapid increase between ages 40 and 55 years. Moreover, the
youngest women in the SWHS cohort were, in general, the most
highly exposed. Of women who were 20–30 years of age
at interview, 68% had serum TCDD levels > 100 ppt. Many
of these women may not have had sufficient time for the effects
of TCDD, if any, to become clinically manifest. Thus, it will
be important to continue to follow the SWHS cohort."
also discuss animal experiments indicating the most sensitive stages
to disruption of mammary gland development by dioxin occur in the
womb and post-natally through to sexual maturity. As Warner et
al.'s research only covered the first 18 years post-explosion,
girls exposed in Seveso to dioxin before puberty have not yet reached
the age of highest incidence of breast cancer. This would suggest
that the SWHS study has not yet observed the effect of dioxin
on those in the most vulnerable stages of development when exposure
unstated implication of these two observations is that, if the link
that they observed between dioxin and breast cancer risk is not
a statistical fluke, then the association should become stronger
as the cohort ages, making it imperative to continue this research.
the meantime, this result adds additional weight to the urgency
for the US EPA to release its dioxin
reassessment and initiate stronger protective standards on dioxin