Association between circulating levels of IGF-1 and IGFBP-3 and lung cancer risk: a meta-analysis

PLoS One. 2012;7(11):e49884. doi: 10.1371/journal.pone.0049884. Epub 2012 Nov 19.


Background: The insulin-like growth factor (IGF) system was documented to play a predominant role in neoplasia. As lung cancer is one of the most malignant cancers, we conducted a meta-analysis in order to investigate the strength of association between circulating IGF-1 and IGFBP-3 levels and lung cancer.

Methodology/principal findings: A systematic literature search was conducted to identify all prospective case-control studies and case-control studies on circulating IGFs and IGFBPs levels. Six nested case-control studies (1 043 case subjects and 11 472 control participants) and eight case-control studies (401 case subjects and 343 control participants) were included in this meta-analysis. Pooled measure was calculated as the inverse variance-weighted mean of the natural logarithm of multivariate adjusted OR with 95% CIs for highest vs. lowest levels to assess the association of circulating IGF-1 and IGFBP-3 concentrations and lung cancer. Standard mean difference (SMD) was also calculated to indicate the difference of the circulating IGF-1 and IGFBP-3 concentrations between the lung cancer case group and the control group. Of the nested case-control studies, ORs for the highest vs. lowest levels of IGF-1 and IGFBP-3 were 1.047 (95% CI: [0.802,1.367], P = 0.736) and 0.960 (95%CI: [0.591,1.559], P = 0.868) respectively; and SMDs were -0.079 (95%CI:[ -0.169, 0.011], P = 0.086) and -0.097 (95%CI:[ -0.264,0.071], P = 0.258) for IGF-1 and IGFBP-3 respectively. As to the case-control studies, SMDs were 0.568 (95%CI:[ -0.035, 1.171], P = 0.065) and -0.780 (95%CI:[ -1.358, -0.201], P = 0.008) for IGF-1 and IGFBP-3 respectively.

Conclusions/significance: Inverse association was shown between IGFBP-3 and lung cancer in the case-control studies,and the circulating level of IGFBP-3 underwent a decline during tumorogenesis and development of lung cancer, which suggested IGFBP-3 a promising candidate for the biomarker of lung cancer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Cell Transformation, Neoplastic
  • Genetic Association Studies*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3* / blood
  • Insulin-Like Growth Factor Binding Protein 3* / genetics
  • Insulin-Like Growth Factor I / genetics*
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Risk Factors


  • Biomarkers, Tumor
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I

Grant support

This study was supported by Provincial natural science foundation of Shandong (ZR2010HM067 and ZR2011HM077) and Provincial Science and Technology Development Planning of Shandong (2011GGH21819).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.