Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers

Gloria Y.F. Ho, Siqun L. Zheng, Mary Cushman, Roman Perez-Soler, Mimi Kim, Xiaonan Xue, Tao Wang, Nicolas F. Schlecht, Lesley Tinker, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Robert Wallace, Chu Chen, Jianfeng Xu, Herbert Yu

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background: The epidermal growth factor receptor (EGFR) signaling network is involved in lung carcinogenesis. This study examined whether ligands that activate or suppress the EGFR signaling network were associated with lung cancer risk in ever smokers. Methods: A nested case-control study within the Women's Health Initiative assessed baseline plasma levels of insulin, insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-3, interleukin (IL)-6, hepatocyte growth factor (HGF), and nerve growth factor (NGF) in 1143 ever-smoking lung cancer cases and 1143 controls. Leptin was measured as an adiposity biomarker. Conditional logistic regression was used in data analyses. Results: Leptin was inversely associated with lung cancer risk (odds ratio [ORcontinuous] per Ln [pg/mL] = 0.85, 95% confidence interval [CI] = 0.74 to 0.98). After adjusting for adiposity and other risk factors, null associations were found for IL-6, HGF, and NGF. In current smokers, but not former smokers, high insulin levels were associated with increased lung cancer risk (OR for 4th quartile vs others [ORq4] = 2.06, 95% CI = 1.30 to 3.26) whereas IGFBP-3 had a linear inverse association (ORcontinuous per ×mu;g/mL = 0.64, 95% CI = 0.41 to 0.98). The insulin association was consistent across subgroups defined by body mass index and histological type, but the IGFBP-3 association was specific to small cell lung cancer. There was a modest positive association between IGF-1 and lung cancer risk in current smokers (ORq4 = 1.44, 95% CI = 0.90 to 2.29). Conclusions: Independent of obesity, high insulin levels but reduced levels of IGFBP-3 were associated with increased lung cancer risk in current smokers.

Original languageEnglish (US)
Article numberdjw012
JournalJournal of the National Cancer Institute
Volume108
Issue number7
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers'. Together they form a unique fingerprint.

Cite this