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Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort.

Abstract

Recent prospective studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers. We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk, with a 2-fold increased risk in the highest quartile. We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers. We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case (final number, 297) could be matched from the same study arm on age (within 5-year intervals), sex, ethnicity, year of enrollment into the beta-Carotene and Retinol Efficacy Trial, year of blood draw, and exposure category (smoking or asbestos). The cases were significantly heavier smokers than the controls (mean pack-years, 58.7 and 45.9, respectively; P < 0.001). An inverse relationship between IGF-I level and age was evident only for former smokers, and not for those who were current smokers at the time of blood draw. Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls, but none of the differences achieved statistical significance. The odds ratios for IGF-I were around unity, except for subsets of heaviest smokers and those who had quit smoking for the longest period of time, in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile (odds ratios, 2.21-2.91), although again, none achieved statistical significance. For younger subjects, IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3. Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level, and these tended to be higher in current smokers and more recent quitters. These results do not support the conclusions of our prior case-control study. It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels (notably in younger subjects with higher baseline levels) that may obscure a relatively modest association between IGF-I level and lung cancer risk. On the other hand, risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters. This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation. Finally, from these data, we cannot exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels.

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  • Authors+Show Affiliations

    ,

    Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. mspitz@mdanderson.org

    , , , ,

    Source

    MeSH

    Aged
    Antioxidants
    Biomarkers, Tumor
    Case-Control Studies
    Double-Blind Method
    Female
    Humans
    Insulin-Like Growth Factor Binding Protein 3
    Insulin-Like Growth Factor I
    Lung Neoplasms
    Male
    Middle Aged
    Odds Ratio
    Prevalence
    Risk Factors
    Smoking
    Statistics as Topic
    Treatment Outcome
    United States
    Vitamin A
    beta Carotene

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Evaluation Studies
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12433720

    Citation

    Spitz, Margaret R., et al. "Serum Insulin-like Growth Factor (IGF) and IGF-binding Protein Levels and Risk of Lung Cancer: a Case-control Study Nested in the beta-Carotene and Retinol Efficacy Trial Cohort." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 11, no. 11, 2002, pp. 1413-8.
    Spitz MR, Barnett MJ, Goodman GE, et al. Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. Cancer Epidemiol Biomarkers Prev. 2002;11(11):1413-8.
    Spitz, M. R., Barnett, M. J., Goodman, G. E., Thornquist, M. D., Wu, X., & Pollak, M. (2002). Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 11(11), pp. 1413-8.
    Spitz MR, et al. Serum Insulin-like Growth Factor (IGF) and IGF-binding Protein Levels and Risk of Lung Cancer: a Case-control Study Nested in the beta-Carotene and Retinol Efficacy Trial Cohort. Cancer Epidemiol Biomarkers Prev. 2002;11(11):1413-8. PubMed PMID: 12433720.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. AU - Spitz,Margaret R, AU - Barnett,Matt J, AU - Goodman,Gary E, AU - Thornquist,Mark D, AU - Wu,Xifeng, AU - Pollak,Michael, PY - 2002/11/16/pubmed PY - 2003/3/8/medline PY - 2002/11/16/entrez SP - 1413 EP - 8 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 11 IS - 11 N2 - Recent prospective studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers. We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk, with a 2-fold increased risk in the highest quartile. We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers. We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case (final number, 297) could be matched from the same study arm on age (within 5-year intervals), sex, ethnicity, year of enrollment into the beta-Carotene and Retinol Efficacy Trial, year of blood draw, and exposure category (smoking or asbestos). The cases were significantly heavier smokers than the controls (mean pack-years, 58.7 and 45.9, respectively; P < 0.001). An inverse relationship between IGF-I level and age was evident only for former smokers, and not for those who were current smokers at the time of blood draw. Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls, but none of the differences achieved statistical significance. The odds ratios for IGF-I were around unity, except for subsets of heaviest smokers and those who had quit smoking for the longest period of time, in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile (odds ratios, 2.21-2.91), although again, none achieved statistical significance. For younger subjects, IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3. Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level, and these tended to be higher in current smokers and more recent quitters. These results do not support the conclusions of our prior case-control study. It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels (notably in younger subjects with higher baseline levels) that may obscure a relatively modest association between IGF-I level and lung cancer risk. On the other hand, risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters. This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation. Finally, from these data, we cannot exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/12433720/Serum_insulin_like_growth_factor__IGF__and_IGF_binding_protein_levels_and_risk_of_lung_cancer:_a_case_control_study_nested_in_the_beta_Carotene_and_Retinol_Efficacy_Trial_Cohort_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=12433720 DB - PRIME DP - Unbound Medicine ER -