Maternal reproductive hormones and angiogenic factors in pregnancy and subsequent breast cancer risk
- 23 Downloads
Breast cancer risk associated with pregnancy characteristics may be mediated by maternal hormones or angiogenic factors.
We conducted a prospective breast cancer case-control study among women in the Avon Longitudinal Study of Parents and Children (ALSPAC) and Norwegian Mother and Child Cohort Study (MoBa) related to maternal pregnancy prolactin (n = 254 cases and 374 controls), placental growth factor (PlGF, n = 252 and 371), soluble fms-like tyrosine kinase-1 (sFlt-1, n = 118 and 240) and steroid hormone concentrations (ALSPAC only, n = 173 and 171). Odds ratios (OR) and 95% confidence intervals (CI) for a 1 SD change in analytes were estimated using unconditional logistic regression with matching factors (cohort, mother’s birth year, serum/plasma, blood collection timing) and gestational age.
Breast cancer ORs (95% CI) were 0.85 (0.51–1.43) for estradiol, 0.86 (0.67–1.09) for testosterone, 0.89 (0.71–1.13) for androstenedione, 0.97 (0.71–1.34) for hCG, 0.93 (0.75, 1.15) for prolactin, 1.00 (0.78–1.27) for PlGF and 1.91 (1.00–3.65 ALSPAC) and 0.94 (0.73–1.21 MoBa) for sFlt-1, and were similar adjusting for potential confounders. Results were similar by blood collection timing, parity, age at first birth or diagnosis, and time between pregnancy and diagnosis.
These data do not provide strong evidence of associations between maternal hormones or angiogenic factors with subsequent maternal breast cancer risk.
KeywordsPregnancy Estrogens Androgens Hormones Angiogenic factors Breast cancer ALSPAC MoBa
We are extremely grateful to all the ALSPAC and MoBa families who take part in these ongoing studies, the midwives for their help in recruiting them, and the entire study teams in the UK and Norway (including interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses). This publication is the work of the authors who will serve as guarantors for the contents of this paper. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. AB’s and RC’s contributions were funded by the Wellcome Trust (Grant ref: WT086118/Z/08/Z). DAL’s contribution to this paper was supported by the NIHR Biomedical Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. DAL works in a Unit that receives support from the University of Bristol and the UK Medical Research Council (MC_UU_1201/5) and she is a NIHR Senior Investigator (NF-SI-0166-10196). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537- 01 and grant no.2 UO1 NS 047537-06A1). ACS’s contribution to the paper was supported by Oslo University Hospital, the Division of Obstetrics and Gynecology. The National Cancer Institute provided intramural funds to perform the assays and to support RT’s and MH’s research time. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this paper are those of the authors and not necessarily those of the UK Medical Research Council, National Health Service, National Institute for Health Research, or Department of Health, or any other funder listed above.
Compliance with ethical standards
Conflict of interest
DAL has received support from Roche Diagnostics, Medtronic, UK, EU, and US government funding bodies and UK charities for research unrelated to that presented in this paper. All other authors declare no conflict of interest regarding support for the work under consideration, or for other projects, either financial or in kind from any third party, company or organisation whose finances or reputation may be affected by the publication of the work; any recent, existing or planned employment relationship or consultancy (whether paid or unpaid) any of the authors has with an organisation whose finances or reputation may be affected by the publication of the work; or any direct financial interest any of the authors or their spouses, parents or children has (personal shareholdings, consultancies, patents or patent applications) whose value could be affected by the publication.
The current analysis makes secondary use of pre-existing data from ALSPAC and MoBa participants who provided written informed consent.
Research involving human participants
Ethical approval in ALSPAC was obtained from the ALSPAC Ethics and Law Committee and NHS Research Ethics Committees. Access and use of the linked ALSPAC cancer registry information was restricted to AB and RC who are ONS Accredited Researchers operating within the ONS ‘Safe Research’ framework. MoBa has a license from the Norwegian Data Inspectorate (01-4325) and approval from the Regional Committee for Medical Research Ethics (REK), Southern Norway (S-97045, S-95113). The angiogenic factor study received approval from REK, South-Eastern Norway (S-08541a) and a license from the Norwegian Data Inspectorate (08/01126-4). At the U.S. National Cancer Institute, the project was reviewed by the Office of Human Subjects Research and exempted from institutional review board approval on the basis that the analysis was performed in the U.K. using de-identified data.
- 8.Lukanova A, Andersson R, Wulff M, Zeleniuch-Jacquotte A, Grankvist K, Dossus L, Afanasyeva Y, Johansson R, Arslan AA, Lenner P et al (2008) Human chorionic gonadotropin and alpha-fetoprotein concentrations in pregnancy and maternal risk of breast cancer: a nested case-control study. Am J Epidemiol 168:1284–1291CrossRefPubMedCentralGoogle Scholar
- 16.Fortner RT, Tolockiene E, Schock H, Oda H, Lakso H, Hallmans G, Kaaks R, Toniolo P, Zeleniuch-Jacquotte A, Grankvist K et al (2017) Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case-control study in the Northern Sweden maternity cohort. Breast Cancer Res 19:82CrossRefPubMedCentralGoogle Scholar
- 29.Troisi R, Ganmaa D, dos Santos Silva I, Davaalkham D, Rosenberg PS, Rich-Edwards J, Frasier L, Houghton L, Janes C, Stanczyk F et al (2014) The role of hormones in the differences in the incidence of breast cancer between Mongolia and the United Kingdom. PLoS ONE 9:e114455CrossRefPubMedCentralGoogle Scholar
- 32.Fortner RT, Schock H, Kaaks R, Lehtinen M, Pukkala E, Lakso H, Tanner M, Kallio R, Joensuu H, Korpela J et al (2017) Human chorionic gonadotropin does not correlate with risk for maternal breast cancer: results from the finnish maternity cohort. Cancer Res 77:134–141CrossRefPubMedCentralGoogle Scholar
- 37.Pepe G, Albrecht E (2008) Steroid endocrinology of pregnancy. Glob Libr Women’s Med. ISSN: 1756–2228. https://doi.org/10.3843/GLOWM.10311