Circulating Free Insulin-Like Growth Factor (IGF)-I , Total IGF-I, and IGF Binding Protein-3 Levels Do Not Predict the Future Risk to Develop Prostate Cancer: Results of a Case-Control Study Involving 201 Patients within a Population-Based Screening with a 4-Year Interval

Abstract

Recent studies have reported that serum IGF-I levels in the highest quartile of the normal range and IGF binding protein-3 (IGFBP-3) in the lowest quartile of the normal range are associated with an increased risk of future prostate cancer and/or presence of prostate cancer. It has also been suggested that the measurement of circulating total IGF-I concentrations might be a useful tool for the early detection of prostate cancer in men with moderately increased prostate-specific antigen (PSA) levels. To determine whether circulating free IGF-I, total IGF-I, and IGFBP-3 levels can predict future prostate cancer risk, we prospectively studied prostate cancer characteristics in a cohort of men during two rounds (mean interval, 4 yr) of a population-based screening study for prostate cancer. Two hundred one prostate cancer cases were detected at the second-round screening (aged 55-70 yr), and all these subjects were enrolled in the case group for the present study. Prostate cancer had been confirmed by biopsy in all cases. These 201 subjects were matched with the 201 nonprostate cancer cases by age, serum PSA range at the first-round screening (PSA < 2 ng/ml, n = 67; PSA = 2-3 ng/ml, n = 67; and PSA = 3-4 ng/ml, n = 67), and residence area. At baseline, total IGF-I, free IGF-I, and IGFBP-3 levels and prostate volume of cases with prostate cancer were not different from those of healthy controls. PSA velocity was significantly different between cases and controls (P < 0.001).Stepwise forward logistic regression analysis showed that only PSA levels at baseline and PSA at round 2 after 4 yr are good predictors of prostate cancer, whereas total IGF-I, free IGF-I, and IGFBP-3 did not predict the development of prostate cancer. Only one of the 201 subjects with prostate cancer had metastases. Within the subjects with prostate cancer, there were no differences of IGF-I parameters with different tumor node metastasis categories and/or Gleason scores. Our study suggests that the measurement of serum IGF-I and/or IGFBP-3 concentrations in addition to PSA does not improve the identification of men at high risk to develop early stages of prostate cancer. In addition, our results indicate that the endocrine IGF-I system is not directly involved in the growth of the early stages of prostate cancer.

Combination of insulin-like growth factor-1, IGF binding protein-3, chromogranin A and prostate specific antigen can improve the detection of prostate cancer

“…Similarly, some earlier reports found disappointing results for these biomarkers. [42] Although the negative findings of the present study regarding IGF-1, IGFBP-3 or CgA serum levels in differentiating between the PCa and control groups; are notable, analysing the combination of these markers with PSA either in the PCa and control groups revealed that their combinations with serum tPSA level, (IGF-1/tPSA, IGFBP-3/tPSA and CgA/tPSA) were differentiated significantly among PCa, BPH patients and healthy individuals. These combinations could, potentially, effectively distinguish PCa patients from non-malignant individuals.…”

Serum Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-3 Concentrations and Prostate Cancer Risk: Results from the European Prospective Investigation into Cancer and Nutrition

“…A few prospective studies have reported null associations between serum IGF-I concentration and total prostate cancer risk, but with the exception of the Melbourne Collaborative Cohort Study (15), these were based on small numbers of cases (i.e., <200 cases; refs. 10,11,14,19,20).…”

“…This variation may be important because evidence from a metaanalysis of six epidemiologic studies suggests that elevated levels of serum IGF-I, expressed either as absolute concentrations or relative to levels of IGFBP-3, may be associated with an increased risk of prostate cancer (9), although findings from more recent prospective studies (10)(11)(12)(13)(14)(15)(16)(17) and studies not included in the meta-analysis (18)(19)(20) are inconsistent. In particular, there is growing evidence that serum IGF-I levels are more strongly associated with advanced-stage disease than localized disease (12,17,18), suggesting that IGF-I may be associated with tumor aggressiveness.…”

Relationship of Dietary Protein and Soy Isoflavones to Serum IGF-1 and IGF Binding Proteins in the Prostate Cancer Lifestyle Trial

“…Conversely, there is some evidence that two of the main IGF-1 binding proteins (IGFBPs), IGFBP-1 and IGFBP-3, may be protective (4)(5)(6)(7)(8). In fact, individuals with both the highest levels of IGF-1 and the lowest levels of IGFBP-3 may be those at 40 highest risk (4).…”

“…Although patients with prostate cancer show levels of IGF-1 that are approximately 8% higher than men without prostate 320 cancer (37), we are not aware of any studies describing the progression of circulating IGF-1 over time in patients with early-stage prostate cancer. In addition, although an association between IGF-1 and risk of prostate cancer has been observed, the predictive value of plasma concentrations of 325 IGF-1 and its binding proteins in the prognosis of prostate cancer is still being debated (4,(37)(38)(39)(40).…”