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 (Nan) Xue, Tao Wang, Nicolas F. Schlecht, Lesley Tinker, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Robert Wallace, Chu Chen, Jianfeng Xu, Herbert Yu

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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

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Insulin-Like Growth Factor Binding Protein 3
Lung Neoplasms
Insulin
Confidence Intervals
Hepatocyte Growth Factor
Adiposity
Nerve Growth Factor
Somatomedins
Leptin
Epidermal Growth Factor Receptor
Interleukin-6
Odds Ratio
Small Cell Lung Carcinoma
Women's Health
Case-Control Studies
Carcinogenesis
Body Mass Index
Obesity
Biomarkers
Logistic Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers. / Ho, Gloria Y F; Zheng, Siqun L.; Cushman, Mary; Perez-Soler, Roman; Kim, Mimi; Xue, Xiaonan (Nan); Wang, Tao; Schlecht, Nicolas F.; Tinker, Lesley; Rohan, Thomas E.; Wassertheil-Smoller, Sylvia; Wallace, Robert; Chen, Chu; Xu, Jianfeng; Yu, Herbert.

In: Journal of the National Cancer Institute, Vol. 108, No. 7, djw012, 2016.

Research output: Contribution to journalArticle

Ho, GYF, Zheng, SL, Cushman, M, Perez-Soler, R, Kim, M, Xue, XN, Wang, T, Schlecht, NF, Tinker, L, Rohan, TE, Wassertheil-Smoller, S, Wallace, R, Chen, C, Xu, J & Yu, H 2016, 'Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers', Journal of the National Cancer Institute, vol. 108, no. 7, djw012. https://doi.org/10.1093/jnci/djw012
Ho, Gloria Y F ; Zheng, Siqun L. ; Cushman, Mary ; Perez-Soler, Roman ; Kim, Mimi ; Xue, Xiaonan (Nan) ; Wang, Tao ; Schlecht, Nicolas F. ; Tinker, Lesley ; Rohan, Thomas E. ; Wassertheil-Smoller, Sylvia ; Wallace, Robert ; Chen, Chu ; Xu, Jianfeng ; Yu, Herbert. / Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 7.
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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.",
author = "Ho, {Gloria Y F} and Zheng, {Siqun L.} and Mary Cushman and Roman Perez-Soler and Mimi Kim and Xue, {Xiaonan (Nan)} and Tao Wang and Schlecht, {Nicolas F.} and Lesley Tinker and Rohan, {Thomas E.} and Sylvia Wassertheil-Smoller and Robert Wallace and Chu Chen and Jianfeng Xu and Herbert Yu",
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T1 - Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers

AU - Ho, Gloria Y F

AU - Zheng, Siqun L.

AU - Cushman, Mary

AU - Perez-Soler, Roman

AU - Kim, Mimi

AU - Xue, Xiaonan (Nan)

AU - Wang, Tao

AU - Schlecht, Nicolas F.

AU - Tinker, Lesley

AU - Rohan, Thomas E.

AU - Wassertheil-Smoller, Sylvia

AU - Wallace, Robert

AU - Chen, Chu

AU - Xu, Jianfeng

AU - Yu, Herbert

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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