Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort

doi:10.1136/bmj.326.7383.248

BMJ 2003;326:248 ( 1 February )

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Fetal growth and subsequent risk of breast cancer: results from long term follow up of Swedish cohort

V A McCormack, research fellow, ^a I dos Santos Silva, clinical senior lecturer, ^a B L De Stavola, senior lecturer, ^a R Mohsen, programmer, ^b D A Leon, professor, ^a H O Lithell, professor. ^b

^a Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, ^b Department of Geriatrics, Uppsala University, PO Box 609, S751-25 Uppsala, Sweden

Correspondence to: V A McCormack
valerie.mccormack{at}lshtm.ac.uk

Objective: To investigate whether size at birth and rateof fetal growth influence the risk of breast cancer inadulthood.
Design: Cohort identified from detailed birth records,with 97% followup.
Setting: Uppsala Academic Hospital,Sweden.
Participants: 5358 singleton females born during 1915-29,alive and traced to the 1960census.
Main outcome measures: Incidence of breast cancer before (at age<50 years) and after ( $>=$ 50 years) themenopause.
Results: Size at birth was positively associated withrates of breast cancer in premenopausal women. In women who weighed $>=$ 4000 g at birth rates of breast cancer were 3.5 times (95% confidenceinterval 1.3 to 9.3) those in women of similar gestational agewho weighed <3000 g at birth. Rates in women in the top fifthsof the distributions of birth length and head circumference were3.4 (1.5 to 7.9) and 4.0 (1.6 to 10.0) times those in the lowestfifths (adjusted for gestational age). The effect of birth weightdisappeared after adjustment for birth length or head circumference,whereas the effects of birth length and head circumference remainedsignificant after adjustment for birth weight. For a given sizeat birth, gestational age was inversely associated with risk (P=0.03for linear trend). Adjustment for markers of adult risk factorsdid not affect these findings. Birth size was not associated withrates of breast cancer in postmenopausalwomen.
Conclusions: Size at birth, particularly length and headcircumference, is associated with risk of breast cancer in womenaged <50 years. Fetal growth rate, as measured by birth size adjustedfor gestational age, rather than size at birth may be the aetiologicallyrelevant factor in premenopausal breastcancer.

What is already known on this topic
There is some evidence that birth weight is related to risk of breast cancer

The exact nature of any association and whether it differs at premenopausal and postmenopausal ages is unclear

Few studies have examined the effect of other measures of birth size and of gestational age

What this study adds
There are strong positive associations between measures of birth size and rates of breast cancer at premenopausal ages that persisted after adjustment for adult risk factors

For a given birth size, gestational age was inversely associated with risk, suggesting that the rate of fetal growth may be aetiologically relevant to premenopausal breast cancer

There was no association between birth characteristics and rates of breast cancer at postmenopausal ages

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Big baby girls have higher breast cancer risk
BMJ 2003 326: 0. [Full Text]

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