***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 —Insulin-like growth factor I ( IGF-I ) has been suggested to be involved in the pathogenesis of atherosclerosis . We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of  ischemic heart disease ( IHD ) . Methods and Results —We conducted a nested case-control study within a large prospect i ve study on cardiovascular epidemiology ( DAN-MONICA ) . We measured  IGF-I and IGFBP-3  in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age , sex , and calendar time . At baseline when all individuals were free of disease , subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period , with a relative risk ( RR ) of 1.94 ( 95 % CI , 1.03 to 3.66 ) of IHD compared with the high IGF-I quartile group , when IGFBP-3 , body mass index , smoking , menopause , diabetes , and use of antihypertensives were controlled for . Conversely , individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 ( 95 % CI , 1.18 to 3.95 ) of having IHD . Identification of a high-risk population with low IGF-I and high IGFBP-3 levels result ed in markedly higher risk of IHD ( RR 4.07 ; 95 % CI , 1.48 to 11.22 ) compared with the index group . Conclusions —Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period . Our findings suggest that IGF-I may be involved in the pathogenesis of IHD Background : Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and , in particular , with an increased risk of advanced-stage prostate cancer . Methods : We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 ( IGFBP-3 ) and prostate cancer risk in a case-control study nested in the European Prospect i ve Investigation into Cancer and Nutrition . This study includes 630 incident prostate cancer cases and 630 matched control subjects .  Odds ratios and their 95 % confidence intervals ( 95 % CI ) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression . Results : The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 ( 95 % CI , 0.99 - 1.82 ; Ptrend = 0.08 ) for IGF-I , 1.39 ( 95 % CI , 1.02 - 1.89 ; Ptrend = 0.12 ) for the IGF-I residuals after adjusting for IGFBP-3 , 1.22 ( 95 % CI , 0.92 - 1.64 ; Ptrend = 0.38 ) for IGFBP-3 , and 1.01 ( 95 % CI , 0.74 - 1.37 ; Ptrend = 0.75 ) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease , although the association of serum IGF-I concentration with risk was slightly stronger for advanced-stage disease ; the odds ratio for the highest versus the lowest third was 1.65 ( 95 % CI , 0.88 - 3.08 ; Ptrend = 0.21 ) for IGF-I and 1.76 ( 95 % CI , 0.92 - 3.40 ; Ptrend = 0.11 ) for IGF-I adjusted for IGFBP-3 . Conclusions : In this large nested case-control study , serum IGF-I concentration is not strongly associated with prostate cancer risk , although the results are compatible with a small increase in risk , particularly for advanced-stage disease ; no association for IGFBP-3 was observed . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1121–7 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 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 cancer Some recent epidemiologic studies have failed to confirm positive associations between insulin-like growth factor-I ( IGF-I ) and the risk of prostate cancer observed in earlier studies but have reported suggestive evidence for a positive association between IGF-binding protein-3 ( IGFBP-3 ) and prostate cancer risk , a result contradicting the earlier assumption that high levels of IGFBP-3 would be protective against prostate cancer . We tested the association between IGF-I and IGFBP-3 and prostate cancer risk by measuring the two peptides in plasma sample s collected at baseline in a prospect i ve cohort study of 17,049 men . We used a case-cohort design , including 524 cases diagnosed during a mean of 8.7 years follow-up and a r and omly sample d subcohort of 1,826 men . The association between each peptide level and prostate cancer risk was tested using Cox models adjusted for country of birth and alcohol consumption . The risk of prostate cancer was not associated with baseline levels of IGF-I or the molar ratio IGF-I/IGFBP-3 ( all odds ratios are between 0.82 and 1.08 ; Ptrend ≥ 0.2 ) , whereas the risk increased with baseline levels of IGFBP-3 ( Ptrend = 0.008 ) , the hazard ratio ( HR ) associated with a doubling of the concentration of IGFBP-3 being 1.70 ( 95 % confidence interval , 1.15 - 2.52 ) . The HR for quartile 4 relative to quartile 1 of IGFBP-3 was 1.49 ( 95 % confidence interval , 1.11 - 2.00 ) . The HRs did not differ by tumor aggressiveness or age at onset ( all Ps ≥ 0.4 ) . In our study , high levels of IGFBP-3 but not IGF-I were associated with an increased risk of prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2006;15(6):1137–41 Insulin-like growth factors ( IGFs ) have potent mitogenic and antiapoptotic effects on prostate epithelial cells . Through modulation of IGF bioactivity and other mechanisms , IGF-binding proteins ( IGFBPs ) also have growth-regulatory effects on prostate cells . Recently , IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western population s. To assess whether IGF-I , IGF-II , IGFBP-1 , or IGFBP-3 are also associated with prostate cancer in a low-risk population , we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 r and omly selected population controls in Shanghai , China . Relative to the lowest quartile of IGF-I levels , men in the highest quartile had a 2.6-fold higher prostate cancer risk , with a significant trend [ odds ratio ( OR ) = 2.63 ; 95 % confidence interval ( 95 % CI ) = 1.19 - 5.79 ; P(trend ) = 0.01 ] . In contrast , men in the highest quartile of IGFBP-3 levels had a 46 % decreased risk relative to the lowest quartile ( OR = 0.54 ; 95 % CI = 0.26 - 1.15 ; P(trend ) = 0.08 ) . A similar but less distinct result was observed for IGFBP-1 ( OR = 0.60 ; 95 % CI = 0.31 - 1.17 ; P(trend ) = 0.25 ) . Men in the highest quartile for the IGF-I : IGFBP-3 molar ratio ( an indirect measure of free IGF-I ) had a 2.5-fold higher risk compared with the lowest quartile ( OR = 2.51 ; 95 % CI = 1.32 - 4.75 , P(trend ) < 0.001 ) . These associations were more pronounced after adjustment for serum 5alpha- and rostane-3alpha,17beta-diol glucuronide 
    Output:
    
For all exposures , there was substantial heterogeneity ( all I(2 ) > 75 % ) , partly explained by study design : the magnitude of associations was smaller in prospect i ve vs. retrospective studies , and for IGFBP-3 , the inverse association with prostate cancer risk was seen in retrospective but not prospect i ve studies .
There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease .
Our meta- analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk .
Associations between IGFBP-3 and prostate cancer were inconsistent , and there was little evidence for a role of IGF-II , IGFBP-1 or IGFBP-2 in prostate cancer risk