Gloria Y F Ho1, Siqun L Zheng1, Mary Cushman1, Roman Perez-Soler1, Mimi Kim1, Xiaonan Xue1, Tao Wang1, Nicolas F Schlecht1, Lesley Tinker1, Thomas E Rohan1, Sylvia Wassertheil-Smoller1, Robert Wallace1, Chu Chen1, Jianfeng Xu1, Herbert Yu1. 1. Affiliations of authors:Department of Occupational Medicine, Epidemiology & Prevention, Feinstein Institute for Medical Research, Northwell Health; Hofstra-Northwell School of Medicine , Great Neck, NY (GYFH); Department of Epidemiology and Population Health (GYFH, MK, XX, TW, NFS, TER, SWS) and Department of Medicine (RPS, NFS), Albert Einstein College of Medicine, Bronx, NY; Center for Genomics and Personalized Medicine Research, Wake Forest University , Winston-Salem, NC (SLZ); Departments of Medicine & Pathology, University of Vermont , Burlington, VT (MC); Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA (LT, CC); Department of Epidemiology, College of Public Health, University of Iowa , Iowa City, IA (RW); NorthShore University HealthSystem , Evanston, IL (JX); University of Hawaii Cancer Center , Honolulu, HI (HY).
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 μg/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.
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 μg/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.
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