Birth Size and Breast Cancer Risk
Isabel dos Santos Silva* , Bianca De Stavola , Valerie McCormack, Collaborative Group on Pre-Natal Risk Factors and Subsequent Risk of Breast Cancer Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom
Background
Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association.
Methods and Findings
Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution.
Conclusions
This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.
Funding: Funding was obtained from Cancer Research UK (CR-UK) programme grant (C150/A5660) to IdSS. CR-UK Training Fellowship (C14292/A5609) to VM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Academic Editor: Hans-Olov Adami, Institutionen for Medicinsk Epidemiologi och Biostatistik (MEB), Sweden
Citation: Silva IdS, Stavola BD, McCormack V, Collaborative Group on Pre-Natal Risk Factors and Subsequent Risk of Breast Cancer (2008) Birth Size and Breast Cancer Risk: Re-analysis of Individual Participant Data from 32 Studies. PLoS Med 5(9): e193 doi:10.1371/journal.pmed.0050193
Received: March 19, 2008; Accepted: August 14, 2008; Published: September 30, 2008
Copyright: © 2008 dos Santos Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: BMI, body mass index; CI, confidence interval; PI, ponderal index; RR, relative risk; SD, standard deviation; SES, socioeconomic status
* To whom correspondence should be addressed. E-mail: isabel.silva@lshtm.ac.uk
These authors contributed equally to this work.
