High insulin levels but reduced levels of insulin-like growth factor binding protein (IGFBP)-3 were associated with increased risk for developing lung cancer among current smokers, a study published in the Journal of the National Cancer Institute has shown.1

Because the epidermal growth factor receptor (EGFR) signaling pathway plays a central role in lung carcinogenesis, researchers sought to investigate whether ligands that activate or suppress the EGFR signaling network were associated with lung cancer risk in people who have smoked or continue to smoke.

For the study, researchers analyzed data from 1143 ever-smoking patients with lung cancer and 1143 controls included in the Women’s Health Initiative. Researchers assessed baseline plasma levels of insulin, insulin-like growth factor (IGF)-1, IGFBP-3, interleukin-6, hepatocyte growth factor, and nerve growth factor. Researchers also measured leptin as a biomarker for adiposity.

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Results showed that leptin was inversely associated with lung cancer risk. Therefore, researchers adjusted for adiposity, as well as other risk factors, when examining whether the other ligands were associated with lung cancer risk.

Researchers found that high insulin levels were associated with increased lung cancer risk in current smokers, but not former smokers. In contrast, IGFBP-3 was inversely associated with disease risk.

Subgroup analyses further demonstrated that the association between insulin and lung cancer risk was consistent across subgroups defined by body mass index and histological subtype.

Investigators also observed a modest positive association between IGF-1 and lung cancer risk in current smokers.


1. Ho GY, Zheng SL, Cushman M, et al. Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers [published online ahead of print April 12, 2016]. J Natl Cancer Inst. doi:10.1093/jnci/djw012.