Insulin growth factor (IGF) 1, IGF-binding proteins and ovarian cancer risk: A systematic review and meta-analysis.
BACKGROUND
Insulin resistance (IR) has been implicated in carcinogenesis, but there is no consensus regarding its involvement in ovarian cancer. We performed a systematic review and meta-analysis to evaluate the association between IR and ovarian cancer.


METHODS
Searches were conducted in five databases for studies evaluating IR markers (levels of serum insulin, C peptide, insulin growth factor [IGF] 1 and IGF-binding proteins [IGFBPs], homeostatic model assessment insulin resistance, and quantitative insulin-sensitivity check index) and ovarian cancer risk. Study selection, data extraction and an assessment of risk of bias were performed independently by three researchers. The associations between IR markers and ovarian cancer were quantified as mean differences (MDs) or standardized MDs (SMDs) and their 95% CIs using random-effects models.


RESULTS
Fourteen case-control studies satisfied our inclusion criteria (n=8130). There was little information on IR markers with the exception of the IGF system. Ovarian cancer was associated with lower IGF-1 levels (SMD -0.43ng/mL, 95% CI -0.67 to -0.18; p=0.0006), and lower IGFBP-3 levels (SMD -0.11ng/mL, 95% CI -0.21 to -0.00; p=0.04). However, ovarian cancer was associated with higher levels of IGFBP-2 and IGFBP-1 (MD 527.3ng/mL, 95%CI 473.6, 581.0; p<0.00001, and MD 3.47ng/mL, 95%CI 1.42, 5.52; p=0.0009 respectively). Subgroup analyses by menopausal status and age (≤55 vs >55y) for IGF-1 and IGFBP-3 showed the subgroups were similar, although heterogeneity remained high.


CONCLUSIONS
The evidence suggests that levels of IGF-1 and IGFBP-3 are lower in patients with ovarian cancer. In contrast, higher levels of IGBP-2 and IGBP-1 are found in patients with ovarian cancer.
School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru.
Ximena
X
Gianuzzi
School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru.
Gabriela
G
Palma-Ardiles
School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru.
Wendy
W
Hernandez-Fernandez
Department of Hematology and Oncology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Vinay
V
Pasupuleti
School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru; Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: adrianhernandezdiaz@gmail.com.
Adrian V
AV
Hernandez
Department of Obstetrics and Gynecology, Universidad de Zaragoza Facultad de Medicina and Lozano Blesa University Hospital, Domingo Miral s/n, Zaragoza 50009, Spain.
Faustino R
FR
Perez-Lopez
D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000097:blood*; D012307:Risk Factors
D015415:Biomarkers; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I
IGF-1; IGFBP-3; Insulin resistance; Meta-analysis; Ovarian cancer