Insulin-like growth factor (IGF)-I and its main binding protein, IGFBP-3, modulate
cell growth and survival, and are thought to be important in tumour development. Circulating
concentrations of IGF-I might be associated with an increased risk of cancer, whereas
IGFBP-3 concentrations could be associated with a decreased cancer risk.
We did a systematic review and meta-regression analysis of case-control studies, including
studies nested in cohorts, of the association between concentrations of IGF-I and
IGFBP-3 and prostate, colorectal, premenopausal and postmenopausal breast, and lung
cancer. Study-specific dose-response slopes were obtained by relating the natural
log of odds ratios for different exposure levels to blood concentrations normalised
to a percentile scale.
We identified 21 eligible studies (26 datasets), which included 3609 cases and 7137
controls. High concentrations of IGF-I were associated with an increased risk of prostate
cancer (odds ratio comparing 75th with 25th percentile 1.49, 95% CI 1.14-1.95) and
premenopausal breast cancer (1.65, 1.26-2.08) and high concentrations of IGFBP-3 were
associated with increased risk of premenopausal breast cancer (1.51, 1.01-2.27). Associations
were larger in assessments of plasma samples than in serum samples, and in standard
case-control studies compared with nested studies.
Circulating concentrations of IGF-I and IGFBP-3 are associated with an increased risk
of common cancers, but associations are modest and vary between sites. Although laboratory
methods need to be standardised, these epidemiological observations could have major
implications for assessment of risk and prevention of cancer.