© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 71-76, Copyright © 1997 by Oxford University Press
A Ekbom, CC Hsieh, L Lipworth, HQ Adami and D Trichopoulos
BACKGROUND: The established risk factors for female breast cancer,
including nulliparity, age at first birth, age at menarche, and age at
menopause, do not adequately explain the occurrence pattern of this cancer.
Therefore, additional factors need to be considered to advance our
understanding of the causes of breast cancer. Evidence obtained from
animals and humans indicates that the perinatal period may be particularly
important. Our earlier studies, based on a subsample of the present
investigation, suggested that factors thought to be positively associated
with estrogen levels during pregnancy are positively associated with breast
cancer risk. However, the associated confidence intervals (CIs) were
generally wide, indicating considerable variability in the data. PURPOSE:
We studied a large number of incident breast cancer case patients and
evaluated several perinatal variables in relation to breast cancer risk.
These variables included some not previously studied, such as gestational
age and neonatal jaundice. We also investigated twin membership as a
predictor variable and death from breast cancer, in addition to occurrence
of breast cancer, as an alternative outcome variable. METHODS: Birth
records for all deliveries at five different hospitals in Sweden during the
period from 1874 through 1961 were used to define a large cohort of women.
Incident case patients with breast cancer in this cohort were ascertained
through the National Cancer Registry or the Uppsala Regional Cancer
Registry from 1958 through 1994. In a case-control study nested in the
cohort, we abstracted data from birth records on 1068 women with incident
breast cancer and on 2727 control subjects individually matched to the case
patients on date of birth. We modeled the data through conditional logistic
regression. All P values were derived from two-sided statistical tests.
RESULTS: We found a markedly reduced risk for breast cancer in women whose
mothers had pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22-0.79)
and an excess risk on women who had neonatal jaundice (OR = 2.16; 95% CI =
1.27-3.67) or who were born before 33 weeks of gestation (OR = 3.96; 95% CI
= 1.45-10.81). Compared with the risk for breast cancer in the singleton,
the risk for breast cancer in dizygotic twins was increased, although this
increase was not statistically significant (OR = 1.72; 95% CI = 0.92-3.20).
There was no evidence in these data for a statistically significant or
substantial association of breast cancer risk with birth size indicators
(i.e., weight and length at birth and placental weight). CONCLUSION AND
IMPLICATIONS: Because pregnancy toxemia is associated with low levels of
estrogens and neonatal jaundice, severe prematurity, and dizygotic twins
with high levels of estrogens, our findings suggest that estrogens and
other hormonal factors, known to influence breast cancer risk in the adult,
may also play a critical role during the intrauterine period.
REVIEWS
Intrauterine environment and breast cancer risk in women: a population- based study
Department of Cancer Epidemiology, Uppsala University, Sweden.
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