Biomarkers of Insulin and the Insulin-Like Growth Factor Axis in Relation to Breast Cancer Risk in Chinese Women

Yifei Zhu,1,* Tiange Wang,2,* Jiayi Wu,1 Ou Huang,1 Li Zhu,1 Jianrong He,1 Yafen Li,1 Weiguo Chen,1 Xiaosong Chen,1 Kunwei Shen1 1Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaosong Chen; Kunwei ShenComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaEmail chenxiaosong0156@hotmail.com kwshen@medmail.com.cnBackground: The interplay between biomarkers of insulin and the insulin-like growth factor (IGF) axis in the context of breast cancer risk is unclear.Methods: We measured the concentrations of insulin, C-peptide, IGF1, and IGF binding protein 3 (IGFBP3) and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) index and the IGF1/IGFBP3 ratio among 2536 patients with breast cancer and 2528 patients with benign breast disease recruited from Ruijin Hospital, Shanghai, China, between 2012 and 2017.Results: Multivariable-adjusted odds ratios (ORs) for breast cancer associated with the highest quartiles versus the lowest quartiles of insulin and IGF factors were 1.45 (95% CI, 1.20– 1.75) for insulin, 1.32 (1.08– 1.60) for C-peptide, 1.53 (1.26– 1.85) for HOMA-IR, and 1.27 (1.05– 1.53) for IGF1; these associations did not differ substantially across stratifications of age, body mass index, age at menarche, or menopausal status (all P for interaction > 0.05). In the joint analysis, the highest quartile of IGF1 was associated with the greatest risk of breast cancer in the highest quartiles of insulin (OR, 1.77; 95% CI, 1.29– 2.44), C-peptide (1.60; 1.17– 2.20), and HOMA-IR (1.90; 1.38– 2.62), compared with the risks associated with the combination of the lowest quartiles of IGF1 and each insulin factor. In stratification analysis, the positive association between IGF1 and breast cancer was stronger in the highest quartiles of insulin (P[interaction] = 0.29), C-peptide (P[interaction] = 0.020), and HOMA-IR (P[interaction] = 0.075).Conclusion: Our findings indicate effect modifications of insulin, C-peptide, and insulin resistance on the relationship between IGF1 and breast cancer risk in Chinese women.Keywords: insulin, insulin-like growth factor 1, C-peptide, insulin resistance, breast cancer