title: Associations of Insulin and IGFBP-3 with Lung Cancer Susceptibility in Current Smokers.
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.
authors.affiliation: 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).
authors.forename: Gloria Y F
authors.initials: GYF
authors.lastname: Ho
authors.affiliation: 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).
authors.forename: Siqun L
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: 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).
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: 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).
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Soler
authors.affiliation: 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).
authors.forename: Mimi
authors.initials: M
authors.lastname: Kim
authors.affiliation: 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).
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.affiliation: 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).
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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).
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.affiliation: 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).
authors.forename: Lesley
authors.initials: L
authors.lastname: Tinker
authors.affiliation: 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).
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: 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).
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.affiliation: 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).
authors.forename: Robert
authors.initials: R
authors.lastname: Wallace
authors.affiliation: 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).
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: 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).
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: 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).
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D002908:Chronic Disease; D015986:Confounding Factors, Epidemiologic; D004198:Disease Susceptibility; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000097:blood*; D064887:Observational Studies as Topic; D016017:Odds Ratio; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*; D014481:United States
chemical_list: C066855:HGF protein, human; D007004:Hypoglycemic Agents; C515497:IGFBP3 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; C502240:NGF protein, human; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D020932:Nerve Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors