Circulating insulin-like growth factor-I and prostate cancer risk

Abstract

Methods of predicting a propensity to developing prostate cancer are presented. The method consists of measuring the IGF status of individual. Individuals with high IGF status, as compared with normal reference range values, are at increased risk for developing prostate cancer. More particularly, the IGF status may be determined by measuring IGF-I levels and/or IGFBP-3 levels. High IGF and low IGFBP levels are indicative of a high IGF status. A method of determining the prognosis of existing prostate cancers or of monitoring disease progression involves determining the IGF/PSA status of an individual. Individuals with a high IGF/PSA status (both high IGF status and high PSA levels) tend to develop severe prostate cancer and have a poorer overall prognosis.

What is claimed is:  
     
         1 . A method of predicting increased risk of prostate cancer in an individual, comprising: 
 a) measuring the concentration of insulin-like growth factor (IGF) in a body fluid from an individual; 
 wherein an elevated concentration of IGF above a reference range for IGF indicates an increased risk for prostate cancer.  
   
     
     
         2 . The method of  claim 1 , wherein said body fluid is selected from the group consisting of blood, plasma, serum and seminal fluid.  
     
     
         3 . The method of  claim 1 , wherein said IGF is total IGF, free IGF or complexed IGF.  
     
     
         4 . A method of predicting increased risk of prostate cancer in an individual, comprising: 
 a) measuring the concentration of insulin-like growth factor-I (IGF-I) in a specimen from an individual;    b) measuring the concentration of insulin-like growth factor binding protein-3 (IGFBP-3) in a specimen from said individual; and    c) conducting a multivariate adjustment of the IGF-I concentration relative to the IGFBP-3 concentration to provide an adjusted IGF-I level; 
 wherein the adjusted IGF-I level above a reference range for adjusted IGF-I indicates an increased risk for prostate cancer.  
   
     
     
         5 . The method of  claim 4 , wherein said specimen is selected from the group consisting of blood, plasma, serum and seminal fluid.  
     
     
         6 . The method of  claim 4 , wherein said IGF-I is total IGF-I, free IGF-I or complexed IGF.  
     
     
         7 . The method of  claim 4 , wherein said IGFBP-3 is total IGFPP-3, free IGFBP-3 or complexed IGFBP-3.  
     
     
         8 . A method of predicting increased risk of prostate cancer in an individual, comprising: 
 a) measuring an IGF status in a body fluid from an individual; 
 wherein increases in the IGF status as compared to normal reference values indicates an increased risk for prostate cancer.  
   
     
     
         9 . The method of  claim 8 , wherein the IGF status is measured by measuring both IGF-I and IGFBP-3, IGF-I alone, or IGFBP-3 alone.  
     
     
         10 . The method of  claim 8 , wherein said body fluid is blood, plasma, serum or seminal fluid.  
     
     
         11 . The method of  claim 9 , wherein said IGF-I is total IGF-I, free IGF-I or complexed IGF-I.  
     
     
         12 . A method of predicting increased risk of prostate cancer with a poor prognosis, comprising: 
 a) measuring the concentration of insulin-like growth factor-I (IGF-I) in a specimen from an individual;    b) measuring the concentration of prostate specific antigen (PSA) in a specimen from said individual; and    c) conducting a multivariate adjustment of the IGF-I concentration relative to the PSA concentration to provide an adjusted IGF/PSA value; 
 wherein an adjusted IGF/PSA value above the reference range for adjusted IGF/PSA indicates an increased risk for prostate cancer with a poor prognosis.  
   
     
     
         13 . The method of  claim 12 , wherein said specimen is selected from the group consisting of blood, plasma, serum and seminal fluid.  
     
     
         14 . The method of  claim 12 , wherein said IGF-I is total IGF-I, free IGF-I or complexed IGF-I.  
     
     
         15 . A method of predicting increased risk of severe prostate cancer in an individual, comprising: 
 a) measuring the concentration of insulin-like growth factor-I (IGF-I) in a specimen from an individual;    b) measuring the concentration of insulin-like growth factor binding protein-3 (IGFBP-3) in a specimen from said individual;    c) measuring the concentration of prostate specific antigen (PSA) in a specimen from said individual; and    d) conducting a multivariate adjustment of the IGF-I concentration relative to the IGFBP-3 concentration and PSA concentration to provide an adjusted IGF/IGFBP/PSA value; 
 wherein an adjusted IGF/IGFBP/PSA value above the reference range for adjusted IGF/IGFBP/PSA indicates an increased risk for severe prostate cancer.  
   
     
     
         16 . The method of  claim 15 , wherein said specimen is selected from the group consisting of blood, plasma, serum and seminal fluid.  
     
     
         17 . The method of  claim 15 , wherein said IGF-I is total IGF-I, free IGF-I or complexed IGF-I.  
     
     
         18 . The method of  claim 15 , wherein said IGFBP-3 is total IGFPP-3, free IGFBP-3 or complexed IGFBP-3.  
     
     
         19 . A method of treating prostate cancer, comprising administering an IGF-axis component modulating agent to an individual with prostate cancer.  
     
     
         20 . A method of  claim 18 , wherein said IGF-axis component modulating agent is selected from the group consisting of somatostatin, somatostatin analogs, and growth hormone releasing antagonists.