***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Plasma levels of insulin-like growth factor-I ( IGF-I ) have been associated with the risk of prostate cancer . However , the association of IGF-I with specific tumor stage and grade at diagnosis , which correlate with risk of recurrence and mortality , has not been studied rigorously . To determine whether plasma levels of IGF-I and its main circulating binding protein , IGF binding protein-3 ( IGFBP-3 ) , predict more aggressive forms of prostate cancer , we investigated the association between plasma levels of each and specific stages and grade s of prostate cancer . METHODS We examined 530 case patients and 534 control subjects in a nested case-control study in the prospect i ve Physicians ' Health Study . Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status  . IGF-I and IGFBP-3 were measured in prospect ively collected plasma sample s. Conditional logistic regression models were used to estimate the relative risks ( RRs ) for prostate cancer associated with IGF-I and IGFBP-3 , stratified on grade ( Gleason score > or = 7 versus < 7 ) and stage ( early = stage A or B prostate cancer versus advanced = stage C or D prostate cancer ) . All statistical tests were two-sided . RESULTS Plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer ( RR = 5.1 , 95 % confidence interval [ CI ] = 2.0 to 13.2 for highest versus lowest quartiles of IGF-I ; RR = 0.2 , 95 % CI = 0.1 to 0.6 for highest versus lowest quartiles of IGFBP-3 ) but not of early-stage prostate cancer . Neither was differentially associated with Gleason score . Men with high IGF-I levels and low IGFBP-3 levels had an RR for advanced-stage prostate cancer of 9.5 ( 95 % CI = 1.9 to 48.4 ) compared with men with low levels of both . Combining IGF-I and IGFPB-3 measurements with a st and ard prostate-specific antigen ( PSA ) measurement for prostate cancer screening increased the specificity ( from 91 % to 93 % ) but decreased sensitivity ( from 40 % to 36 % ) compared with measurement of PSA alone . CONCLUSIONS Circulating levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer , but their utility for screening patients with incident prostate cancer may be limited Recent studies have suggested that IGF-I and IGF-binding protein (IGFBP)-3 , in combination with prostate-specific antigen ( PSA ) , may enhance prostate cancer detection . In this study , we sought to determine the effect on the prediction of future prostate cancer occurrence by incorporating ratios of total and free PSA , IGF-I , IGFBP-3 into PSA testing . Within a population -based prospect i ve cohort study , we investigated the validity ( sensitivity and specificity ) of  plasma concentrations of total and free PSA , IGF-I , and IGFBP-3 and combinations thereof , in 114 cases and 97 controls , in the range of 1.75 - 13.5 microg/l for PSA , as used by Khosravi et al. ( See Ref . 7 ) . Validity estimated by the area under the curve in receiver operator characteristics analysis ( with 95 % confidence interval ) for total PSA was 0.78 ( range , 0.71 - 0.84 ) ; total/free PSA , 0.69 ( range , 0.62 - 0.76 ) ; total PSA/IGF-I , 0.72 ( range , 0.65 - 0.79 ) ; free PSA/IGF-I , 0.55 ( range , 0.48 - 0.63 ) ; total PSA/IGFBP-3 , 0.74 ( range , 0.68 - 0.81 ) ; and free PSA/IGFBP-3 , 0.57 ( range , 0.49 - 0.64 ) . Analysis of ratios of IGF-I , IGFBP-3 , and free and total PSA did not improve validity of PSA testing in the prediction of future occurrence of prostate cancer . It is unlikely that these combinations will improve prostate cancer detection Background : The acid-labile subunit ( ALS ) acts in the insulin-like growth ( IGF ) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier . Given the role of the IGF system in prostate cancer , ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability . Methods : We undertook a prospect i ve study nested in the Physicians ' Health Study to examine ALS , free  IGF-I  , and prostate cancer . We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls . We calculated relative risks ( RR ) and 95 % confidence intervals ( 95 % CI ) adjusted for life-style factors , total IGF-I , and IGFBP3 . Results : ALS was positively correlated with total IGF-I ( r = 0.58 ) , IGFBP3 ( r = 0.68 ) , and free IGF-I ( r = 0.36 ) . Comparing highest versus lowest quartiles , we found no association between free IGF-I and prostate cancer risk ( RR , 0.9 ; 95 % CI , 0.6 - 1.3 ) . In contrast , ALS was positively associated with risk among men in the 2nd ( RR , 1.5 ; 94 % CI , 1.0 - 2.3 ) , 3rd ( RR , 1.6 ; 94 % CI , 1.1 - 2.5 ) , and 4th quartiles ( RR , 1.4 ; 94 % CI , 0.9 - 2.1 ) compared with lowest quartile . The association was stronger for advanced stage tumors ( RR , 2.0 ; 94 % CI , 0.8 - 4.6 ) . There was a suggestion of an interaction between ALS and total IGF-I , whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels . Discussion : Plasma ALS is positively associated with prostate cancer risk , and may interact biologically with IGF-I to affect carcinogenesis . These data provide further support for the role of the IGF axis in prostate cancer . Cancer Epidemiol Biomarkers Prev ; 19(2 ) ; A major problem in review ing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways . The purpose of this paper is to exemplify methods by which results expressed either as risks ( or rates ) according to quantlle groups of the quantitative variable or as results derived from a  logistic regression analysis can be reexpressed in a uniform manner , as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study . An important assumption of the methods is that the quantitative variable has an approximately normal distribution , and a way of investigating the appropriateness of this assumption is given . The methods can be applied to both prospect i ve and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality . In some applications , these methods can be used as a precursor to formal meta- analysis , for example , when differential control of potential confounding factors is not a problem . At the least , the methods can be useful either in quantitatively review ing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors ( IGF ) and of IGF-binding proteins ( IGFBP ) and prostate cancer risk . We assessed the association of prediagnostic plasma levels of IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial . The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France . One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period . For each case , four age-matched controls were selected r and omly . Frozen baseline plasma sample s were used to measure IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 . Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk . After controlling for the intervention group in the trial and the other IGF axis variables , the odds ratios and 95 % confidence interval ( 95 % CI ) comparing the upper quartile to the baseline quartile were 1.83 ( 95 % CI , 0.85 - 3.95 ) , 1.05 ( 95 % CI , 0.35 - 3.18 ) , 0.79 ( 95 % CI , 0.39 - 1.58 ) , and 0.42 ( 95 % CI , 0.12 - 1.52 ) for IGF-I , IGF-II , IGFBP-2 , and IGFBP-3 , respectively . More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers . Our results are consistent with those of some previous prospect i ve studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer Circulating concentrations of insulin-like growth factor I ( IGF-I ) and IGF binding proteins ( IGFBP ) have been associated with the risk of several types of cancer . Dietary correlates of IGF-I and IGFBPs are not yet well established . The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I , IGFBP-1 , IGFBP-2 , and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospect i ve Investigation into Cancer and Nutrition .  Diet was assessed using country-specific vali date d dietary question naires .  Serum concentrations of IGF-I , IGFBP-1 , IGFBP-2 and IGFBP-3 were measured , and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex , age , body mass index , smoking status , and alcohol and energy intake . Each 1 SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5 % , 2.4 % , and 3.3 % , respectively ( P for trend < 0.001 for all ) and a decrease in IGFBP-2 of 3.5 % , 3.5 % , and 5.4 % ( P for trend < 0.001 for all ) , respectively . There were no significant associations between the intake of protein or calcium from nondairy sources and IGF-I. The results from this large cross-sectional analysis show that either the intake of dairy protein or calcium is an important dietary determinant of IGF-I and IGFBP-2 concentrations ; however , we suggest that it is more likely to be protein from dairy products . ( Cancer Epidemiol Biomarkers Prev 2009;18(5):1333–40 OBJECTIVE To quantify the level of insulin-like growth factor ( IGF-1 ) in serum and investigate its role in the diagnosis of prostate cancer . METHODS IGF-1 immunoradiometric assay ( IRMA ) was set up and used to determine serum IGF-1 level in patients with prostate cancer ( n = 81 ) , benign prostate hyperplasia ( BPH , n = 55 ) , uroepithelial tumor ( n = 32 ) and healthy male controls ( n = 84 ) . Furthermore , the levels of IGF-1 and prostate-specific antigen ( PSA )  in 38 patients with BPH were determined every three months for one year . RESULTS Linearity was well demonstrated for IGF-1 in the range of 8 - 1000 ng ( r = 0.98 ) , the lowest limit for detecting IGF-1 being 2 mg/L and the mean recovery for detecting IGF-1 being 94.5 % . The within-replicate coefficient of variance ( CV ) of IGF-1 detection was 7.2 % for a higher level ( 382.4 mg/L ) and 4.2 % for a low level ( 32.5 mg/L ) of IGF-1 . Insulin , growth factor or IGF-2 did not interfere with the detection of IGF-1 ( < 3 ml/L ) . There was high level of IGF-1 in patients with prostate cancer than in healthy controls , patients with BPH and uroepithelial tumor ( P < 0.05 ) ; the odds ratio and its 95 % confidence intervals were 2.86 and 1.38 - 5.34 , respectively ; the specificity and sensitivity of IGF-1 determination were 0.68 and 0.58 , respectively ; furthermore , the level of IGF-1 was increased during the development of prostate cancer . CONCLUSIONS These findings demonstrate that IGF-1 may serve prospect ively as an important tumor marker in the diagnosis and prediction of prostate 
    Output:
    
No strong associations were observed for IGF-II , IGFBP-1 or IGFBP-2 with either milk intake or prostate cancer risk .
There was additional evidence to suggest that the suppression of IGF-II can reduce tumor size , and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumor progression .
Conclusion IGF-I is a potential mechanism underlying the observed associations between milk intake and prostate cancer risk