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Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.

ABSTRACT: 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.

SUBMITTER: Rowlands MA

PROVIDER: S-EPMC3272440 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.

Rowlands Mari-Anne MA Holly Jeff M P JM Gunnell David D Donovan Jenny J Lane J Athene JA Hamdy Freddie F Neal David E DE Oliver Steven S Smith George Davey GD Martin Richard M RM

Cancer research 20111121 2

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 110,0 ...[more]

PMID: 22106399

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Project description:BackgroundObesity has been inconsistently linked to prostate cancer, mainly with mortality rather than incidence. Few large-scale studies exist assessing obesity in relation to prostate-specific antigen (PSA)-detected prostate cancer.MethodsWe used cases and stratum-matched controls from the population-based PSA-testing phase of the Prostate testing for cancer and Treatment study to examine the hypothesis that obesity as measured by body mass index (BMI), waist circumference and waist-to-hip ratio (WHR) is associated with increased prostate cancer risk, and with higher tumour stage and grade. In all, 2167 eligible cases and 11 638 randomly selected eligible controls with PSA values were recruited between 2001 and 2008. A maximum of 960 cases and 4156 controls had measurement data, and also complete data on age and family history, and were included in the final analysis. BMI was categorised as <25.0, 25.0-29.9, ≥ 30.0 in kg m(-2).ResultsFollowing adjustment for age and family history of prostate cancer, we found little evidence that BMI was associated with total prostate cancer (odds ratio (OR): 0.83, 95% confidence interval (CI): 0.67, 1.03; highest vs lowest tertile; P-trend 0.1). A weak inverse association was evident for low-grade (OR: 0.76, 95% CI: 0.59, 0.97; highest vs lowest tertile; P-trend 0.045) prostate cancer. We found no association of either waist circumference (OR: 0.94, 95% CI: 0.80, 1.12; highest vs lowest tertile) or waist-to-hip ratio (WHR; OR: 0.93, 95% CI: 0.77, 1.11; highest vs lowest tertile) with total prostate cancer, and in analyses stratified by disease stage (all P-trend>0.35) or grade (all P-trend>0.16).ConclusionGeneral adiposity, as measured by BMI, was associated with a decreased risk of low-grade PSA-detected prostate cancer. However, effects were small and the confidence intervals had limits very close to one. Abdominal obesity (as measured by WHR/waist circumference) was not associated with PSA-detected prostate cancer.

Dataset Information

Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.

Publications

Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.

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