Intrauterine environments and breast cancer risk: meta-analysis and systematic review.
BACKGROUND
Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses.


METHODS
We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results.


RESULTS
We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk.


CONCLUSIONS
Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.
Park
Sue Kyung
SK
Department of Preventive Medicine, Seoul National University College of Medicine, Yeongeon-dong, Jongro-gu, Seoul 110-799, Seoul, Republic of Korea. suepark@snu.ac.kr
Kang
Daehee
D
McGlynn
Katherine A
KA
Garcia-Closas
Montserrat
M
Kim
Yeonju
Y
Yoo
Keun Young
KY
Brinton
Louise A
LA
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012307:Risk Factors
D004967:Estrogens