Cancer Causes & Control

, Volume 24, Issue 5, pp 873–883 | Cite as

Serum insulin and C-peptide concentration and breast cancer: a meta-analysis

  • Philippe AutierEmail author
  • Alice Koechlin
  • Mathieu Boniol
  • Patrick Mullie
  • Geremia Bolli
  • Julio Rosenstock
  • Peter Boyle
Original Paper



Chronic hyperinsulinemia may play a role in breast cancer etiology. We performed a meta-analysis examining whether serum concentrations of insulin and C-peptide are associated with increased breast cancer risk.


We restricted our analyses to prospective studies. After a systematic literature search, we computed summary relative risks (SRRs) and 95 % confidence intervals (95 % CIs) using random effect models applied to the relative risk associated with the highest versus lowest quantile of serum concentrations. We also graphically examined results in order to identify whether dose–response relationships were present.


Six articles including 1,890 cases were retrieved for serum insulin levels and five for serum C-peptide levels including 1,759 cases. SRR and 95 % CI were 1.08 (0.66–1.78) for insulin and 1.04 (0.77–1.41) for C-peptide. Heterogeneity of results between studies was high for insulin and inexistent for C-peptide. Restricting the analysis to women diagnosed with breast cancer before or after menopause did not alter results. In insulin studies, SRR computed from relative risks not adjusted for body mass index (and other risk factors) was 1.22 (0.91–1.63). The SRR fell to 1.02 (0.53–1.97) in studies that adjusted for body mass index and other factors. Similar drops occurred in C-peptide studies, from 1.11 (0.87–1.41) to 1.06 (0.70–1.61). No consistent dose–response relationship was apparent in either pre- or post-menopausal cancers.


Our meta-analysis of observational studies found no evidence of an association between serum insulin or C-peptide concentrations and breast cancer risk. Increased risk found by some studies may have been due to inadequate control for adiposity.


Breast cancer Endogenous insulin C-Peptide Meta-analysis 



This study was part of the research activities of the International Prevention Research Institute (iPRI) Research Group on Diabetes, Metabolic Disorders and Cancer, whose members are: P. Autier, A. Koechlin, M. Boniol, P. Mullie, P. Boyle, F. Valentini, K. Coppens, L.-L. Fairley, M. Boniol, M. Pasterk, M. Smans, M.-P. Curado, M. Bota (iPRI, Lyon, France); S. Gandini (European Institute of Oncology, Milan, Italy); Chris Robertson (Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland); Tongzhang Zheng, Yawei Zhang (Yale University School of Public Health, New Haven, Connecticut, United States of America); Geremia Bolli (Department of Internal Medicine and Oncology, S.M. Misericordia Hospital, University of Perugia, Perugia, Italy); J. Rosenstock (Dallas Diabetes and Endocrine Center, Dallas, United States of America). This study was part of works associated with an unrestricted research grant from Sanofi. None of the authors has received an honorarium for this work and no author has a conflict of interest to declare in relation to the study presented in this article. The corresponding author, Philippe Autier, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest


Supplementary material

10552_2013_164_MOESM1_ESM.ppt (143 kb)
Online Resource 1: Prisma flowchart for literature search on a) insulin and breast cancer, b) c-peptide and breast cancer (PPT 143 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Philippe Autier
    • 1
    Email author
  • Alice Koechlin
    • 1
  • Mathieu Boniol
    • 1
  • Patrick Mullie
    • 1
  • Geremia Bolli
    • 2
  • Julio Rosenstock
    • 3
  • Peter Boyle
    • 1
  1. 1.International Prevention Research InstituteLyonFrance
  2. 2.Department of Medicine, S.M. della Misericordia HospitalUniversity of PerugiaPerugiaItaly
  3. 3.Dallas Diabetes and Endocrine Center at Medical CityDallasUSA

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