title: Circulating levels of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio and colorectal adenomas: A meta-analysis.
abstract: BACKGROUND
  Insulin-like growth factor-1(IGF-1) promotes cell proliferation and inhibits apoptosis, and is thereby implicated in carcinogenesis. Insulin-like growth factor binding protein-3 (IGFBP-3) may antagonize IGF-1 action, leading to inhibition of the potential tumorigenicity of IGF-1. We conducted this meta-analysis to estimate the association between IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio and the risk of colorectal adenomas (CRAs). Further, we investigated whether this association was different between occurrent and recurrent CRA, by adjustment for obesity, and by advanced CRA.
  
  
  METHODS
  Pubmed and Embase were searched up to April, 2015 to identify relevant observational studies and summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI) was estimated using a random-effects model.
  
  
  RESULTS
  A total of 12 studies (11 studies including 3038 cases for IGF-1, 12 studies including 3208 cases for IGFBP-3, and 7 studies including 1867 cases for IGF-1/IGFBP-3 ratio) were included in this meta-analysis. The summary ORs of occurrent CRA for the highest versus lowest category of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio were 1.13 (95% CI: 0.95-1.34), 0.99 (0.84-1.16), and 1.05 (0.86-1.29), respectively. Higher IGF-1 and IGF-1/IGFBP-3 ratio were significantly associated with decreased risk of recurrent CRA (OR for IGF-1=0.60 [95% CI: 0.42-0.85]; IGF-1/IGFBP-3 ratio=0.65 [0.44-0.96]). A stratified analysis by advancement of occurrent CRA produced a significant summary OR of IGF-1 for advanced CRA (OR=2.21 [1.08-4.52]) but not for non-advanced CRA (OR=0.89 [0.55-1.45]). We did not find significant publication bias or heterogeneity.
  
  
  CONCLUSIONS
  Circulating levels of IGF-1, IGFBP-3 and their molar ratio were not associated with the risk of occurrence of CRA, but IGF-1 was associated with the increased risk for occurrence of advanced CRA.
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Family Medicine, Inje University Ilsan Paik Hospital, Goyang-Si, Gyeonggi-Do 411-706, South Korea. Electronic address: yeongsook.yoon@gmail.com.
authors.forename: Yeong Sook
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: nak212@mail.harvard.edu.
authors.forename: NaNa
authors.initials: N
authors.lastname: Keum
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: poxue@channing.harvard.edu.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, RI 02903, USA; Department of Epidemiology, Brown School of Public Health, Providence, RI 02903, USA. Electronic address: hpeyc@channing.harvard.edu.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Cho
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: egiovann@hsph.harvard.edu.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016017:Odds Ratio; D012306:Risk
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
keywords: Advanced adenoma; Colorectal adenoma; Insulin-like growth factor binding protein-3; Insulin-like growth factor-1; Meta-analysis; Neoplasm recurrence