Circulating
insulin-like growth factor-I (
IGF-I) has been studied extensively in
prostate cancer, but there is still little information about IGFs and
IGF-binding proteins (
IGFBP) in
cancers detected by the
prostate-specific antigen (PSA) test. Here, we report the findings of a U.K.-based case-control study to investigate circulating IGFs and IGFBPs in PSA-detected
prostate cancer with regard to their potential associations with different
cancer stages or grades. PSA testing was offered to 110,000 men aged 50 to 69 years from 2002 to 2009. Participants with an elevated level of PSA (≥3.0 ng/mL) underwent prostate biopsy and measurements of blood serum
IGF-I,
IGF-II,
IGFBP-2, and
IGFBP-3 obtained at recruitment. We found that serum levels of
IGF-II (OR per SD increase: 1.16; 95% CI: 1.08-1.24; P(trend) < 0.001),
IGFBP-2 (1.18; 1.06-1.31; P(trend) < 0.01) and
IGFBP-3 (1.27; 1.19-1.36; P(trend) < 0.001), but not
IGF-I (0.99; 0.93-1.04; P(trend) = 0.62), were associated with PSA-detected
prostate cancer. After controlling for
IGFBP-3,
IGF-II was no longer associated (0.99; 0.91-1.08; P(trend) = 0.62) and
IGF-I was inversely associated (0.85; 0.79-0.91; P(trend) < 0.001) with
prostate cancer. In addition, no strong associations existed with
cancer stage or grade. Overall, these findings suggest potentially important roles for circulating
IGF-II,
IGFBP-2, and
IGFBP-3 in PSA-detected
prostate cancer, in support of recent in vitro evidence. Although our findings for
IGF-I agree with previous results from PSA screening trials, they contrast with positive associations in routinely detected disease, suggesting that reducing levels of circulating
IGF-I might not prevent the initiation of
prostate cancer but might, nonetheless, prevent its progression.