Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence.
BACKGROUND
Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer.


METHODS
We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors.


RESULTS
We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]).


CONCLUSIONS
The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.
Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Electronic address: n2fei@channing.harvard.edu.
Fei
F
Xue
Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
Karin B
KB
Michels
D000367:Age Factors; D001724:Birth Weight; D049628:Body Size; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D004054:Diethylstilbestrol / Q000009:adverse effects; D004200:Diseases in Twins / Q000453:epidemiology / Q000209:etiology*; D004461:Eclampsia / Q000453:epidemiology*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000453:epidemiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018570:Risk Assessment; D012307:Risk Factors; D014427:Twins
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol