Association Between Serum Insulin and C-Peptide Levels and Breast Cancer: An Updated Systematic Review and Meta-Analysis

BACKGROUND: Several studies have reported that hyperinsulinemia plays a part in the etiology of breast cancer. However, no consensus has been reached. Therefore, we conducted a meta-analysis to explore the role of insulin and C-peptide in breast cancer. METHODS: A systematic search in PubMed, Embase, and The Cochrane Library was conducted up to September, 2020. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to measure effect sizes. Publication bias was assessed using the Egger test. Stability of these results was evaluated using sensitivity analyses. RESULTS: Fourteen articles including 27,084 cases and five articles including 2,513 cases were extracted for serum insulin levels and C-peptide levels. We found that C-peptide levels were positively associated with breast cancer with overall SMD = 0.37 (95% CI = 0.09–0.65, I(2) = 89.1%). Subgroup analysis by control source illustrated a positive relationship between breast cancer and C-peptide levels in population-based control. Subgroup analysis by C-peptide level indicated a positive correlation between breast cancer and C-peptide levels no matter C-peptide levels in case group is ≤3 ng/ml or >3 ng/ml. Subgroup analysis by age showed that C-peptide level positively correlated to breast cancer in women between the ages of 50 and 60. However, we did not identify any relationship between breast cancer and insulin levels (SMD = 0.22, 95% CI = −0.06–0.50, I(2) = 97.3%). CONCLUSION: This meta-analysis demonstrated that C-peptide levels were positively related to breast cancer in women, and no relationship between insulin levels and breast cancer was found.