Premium
Higher IGFBP3 is associated with increased incidence of colorectal cancer in older men independently of IGF 1
Author(s) -
Chan Yi X.,
Alfonso Helman,
Paul Chubb Stephen Anthony,
Ho Ken K. Y.,
Gerard Fegan Peter,
Hankey Graeme J.,
Golledge Jonathan,
Flicker Leon,
Yeap Bu B.
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13499
Subject(s) - medicine , igfbp3 , prostate cancer , colorectal cancer , oncology , prospective cohort study , cancer , lung cancer , endocrinology , incidence (geometry) , hazard ratio , insulin like growth factor , anabolism , growth factor , confidence interval , physics , receptor , optics
Summary Objective Insulin‐like growth factor 1 ( IGF 1) has anabolic and growth‐promoting effects, raising concerns regarding its potential to promote tumour growth. Circulating IGF 1 is bound to binding proteins, which modulate bioavailability of IGF 1. This study assessed the associations of IGF 1 and its binding proteins 1 ( IGFBP 1) and 3 ( IGFBP 3) with cancer risk. Design A prospective cohort study of 4042 men aged ≥70 years. Methods Plasma total IGF 1, IGFBP 1 and IGFBP 3 were measured between 2001 and 2004. Cancer‐related outcomes were assessed until 20 June 2013 using data linkage. Analyses were performed using proportional hazards models with death as a competing risk, and adjustments were made for potential confounders. Results are expressed as subhazard ratios ( SHR ). Results There were 907 men who were diagnosed with cancer during a median of 9‐year follow‐up. Of these, there were 359, 139 and 125 prostate, colorectal and lung cancers, respectively. After adjustments, total IGF 1 was not associated with the incidence of any cancer, prostate, lung or colorectal cancer. In the fully‑adjusted model, higher IGFBP 3 was associated with increased incidence of colorectal cancer ( SHR = 1.20, 95% CI 1.01‐1.43; P = .041 for every 1 standard deviation increase in IGFBP 3) but not other cancers. This effect was not attenuated by inclusion of total IGF 1 into the multivariate model ( SHR = 1.28, 95% CI 1.03‐1.58; P = .025). Neither total IGF 1, IGFBP 1 nor IGFBP 3 were associated with cancer‐related deaths. Conclusion Higher IGFBP 3 predicted increased incidence of colorectal cancer in older men independent of conventional risk factors and total IGF 1. Further studies are warranted to explore potential underlying mechanisms.