Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank

Cancer Res. 2020 Sep 15;80(18):4014-4021. doi: 10.1158/0008-5472.CAN-20-1281. Epub 2020 Jul 24.


Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias. Higher IGF-I concentration was associated with increased risks of thyroid cancer [HR per 5 nmol/L higher concentration 1.18; 95% confidence interval (CI), 1.01-1.37] in addition to colorectal (HR, 1.08; 95% CI, 1.03-1.13), breast (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.08; 95% CI, 1.05-1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and the possibility that the observed associations may be influenced by reverse causality bias cannot be excluded. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development. SIGNIFICANCE: The results from this outcome-wide analysis are consistent with a positive association of IGF-I with cancers at several sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Specimen Banks
  • Confidence Intervals
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Neoplasms / blood*
  • Neoplasms / etiology
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • United Kingdom


  • IGF1 protein, human
  • Neoplasm Proteins
  • Insulin-Like Growth Factor I