OBSTETRICS
Preeclampsia and subsequent risk of cancer:
update from the Jerusalem Perinatal Study
Ronit Calderon-Margalit, MD, MPH; Yechiel Friedlander, PhD; Rivka Yanetz, PhD; Lisa Deutsch, PhD; Mary C. Perrin, DrPH;
Karine Kleinhaus, MD, MPH; Efrat Tiram, MSc; Susan Harlap, MBBS; Ora Paltiel, MDCM, MSc, FRCPC
OBJECTIVE:
The purpose of this study was to examine the association
between preeclampsia and cancer incidence.
STUDY DESIGN:
The Jerusalem Perinatal Study is a population-based
cohort of all births to 41,206 residents of Western Jerusalem from
1964-76. Cancer incidence to 2004 was assessed by linkage of the
cohort with the Israel Cancer Registry. Cox’s proportional hazards
models were constructed to estimate the hazard ratio for cancer among
women who had had preeclampsia.
RESULTS:
Preeclampsia was associated with a 1.23-fold increased risk of
cancer at all sites, a 37% increased risk of breast cancer, and more than a
doubling of ovarian cancer risk. Analysis by morphologic condition
yielded significantly increased risks for malignancies that were classed as
cystic mucinous and serous (relative risk, 1.96; 95% CI, 1.00-3.83) and
for ductal, lobular, and medullary carcinomas (relative risk, 1.40; 95% CI,
1.07-1.83). No differential association was observed by sex of offspring.
CONCLUSION:
Our study suggests that the previously described pro-
tective effect of preeclampsia on cancer is not universal.
Key words: cancer, cohort, morphologic condition, preeclampsia,
risk, sex
Cite this article as: Calderon-Margalit R, Friedlander Y, Yanetz R, et al. Preeclampsia and subsequent risk of cancer: update from the Jerusalem Perinatal Study.
Am J Obstet Gynecol 2009;200:63.e1-63.e5.
A
growing body of evidence suggests
an association between obstetric
events and long-term morbidity and
death of mothers. Several case-control
studies from the United States
1-4
and a
cohort study from Norway
5
have sug-
gested a decrease in breast cancer risk for
women with a history of preeclampsia.
Recently, 2 reports suggested that this
protective effect was evident only among
preeclamptic women who gave birth to
male offspring.
6,7
Another report from
Norway suggested a decreased risk of all-
cancer deaths for women who were di-
agnosed with preeclampsia and had
had a preterm delivery.
8
Similarly, in a
recently published retrospective co-
hort study from Utah, preeclampsia
was associated with an 8% decrease in
risk of cancer at all sites and a statisti-
cally significant decreased risk of pap-
illary and squamous cell carcinomas
(hazard ratio [HR], 0.74; 95% CI, 0.58-
0.94), irrespective of site.
9
In contrast to these reports, our group
previously published findings from the
Jerusalem Perinatal Study
10
that sug-
gested that women who experienced pre-
eclampsia were at increased risk of can-
cer at all sites (HR, 1.27; 95% CI, 1.03-
1.57), which included cancers of the
breast (HR, 1.38; 95% CI, 1.00-1.89),
ovary, (HR, 2.32; 95% CI, 1.01-5.34),
stomach (HR, 3.10; 95% CI, 1.23-7.84),
and lung or larynx (HR, 2.81; 95% CI,
1.12-7.05).
We recently updated our cancer inci-
dence data to Dec. 31, 2004, which added
175,625 person-years of follow-up eval-
uations. In view of the recent studies,
6,7,9
we aimed to study the association be-
tween preeclampsia and cancer inci-
dence and to further our analysis by
morphologic tumor type and sex of
offspring.
M
ATERIALS AND
M
ETHODS
The Jerusalem Perinatal Study is a pop-
ulation-based research cohort of all
births to residents of Western Jerusalem
and its surroundings between 1964-
1976. The database includes demo-
graphic, obstetric, and neonatal infor-
mation on 92,408 births and 41,206
mothers. Detailed information on data
collection has been described previous-
ly.
11
Briefly, information on all births
was copied from birth notifications; for
92% of participants, data were ab-
stracted also from maternity ward log-
books. Thus, information on pregnancy
complications was complete for 37,927
women. During the cohort inception,
preeclampsia was defined as hyperten-
sion (systolic blood pressure of Ͼ 140
mm Hg and/or diastolic blood pressure
of Ͼ 90 mm Hg), proteinuria, and
edema. Information was recorded per
birth with mothers’ and offsprings’ iden-
From Hebrew University–Hadassah Braun
School of Public Health, Jerusalem, Israel
(Drs Calderon-Margalit, Friedlander,
Yanetz, Deutsch, and Paltiel and Ms Tiram);
the Department of Psychiatry, New York
University School of Medicine, New York,
NY (Drs Perrin and Harlap); and the
Departments of Psychiatry (Dr Kleinhaus)
and Epidemiology (Dr Harlap), Columbia
University, New York, NY.
Received Jan. 8, 2008; accepted June 19,
2008
Reprints: Ronit Calderon-Margalit, MD, MPH,
Hebrew University-Hadassah Braun School of
Public Health, POB 12272, 91120 Jerusalem,
Israel. ronitcm@ekmd.huji.ac.il.
This study was supported by the National
Institutes of Health Grant R01 CA080197.
0002-9378/$36.00
© 2009 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2008.06.057
Research
www.
AJOG
.org
JANUARY 2009 American Journal of Obstetrics & Gynecology
63.e1