***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 
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    ***EXAMPLES*** 
    Input: This is the first study to investigate the associations of IGF-1 , IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer  in prospect ively collected blood sample s from an Oriental population . Between 1986 and 1989 serum sample s were collected at baseline from 18 244 men , aged 45–65 years , without a history of cancer and living in Shanghai , China .  IGF-1 , IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort , who were matched to the index cases by neighbourhood of residence , age , and year and month of sample collection . Serum IGF-1 was not associated with risk of colorectal cancer . IGF-2 and IGFBP-3 , on the other h and , exhibited statistically significant , positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment ( within 8 years ) . After adjustment for body mass index , cigarette smoking and alcohol intake , men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 ( 95 % Cl = 1.67–4.50 ; 2-sided P for trend = 0.0008 ) and 2.85 ( 95 % Cl = 1.69–4.81 ; 2-sided P for trend = 0.01 ) , respectively . Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer . © 2001 Cancer Research Campaign There is some evidence that glucose and other factors related to glucose metabolism , such as insulin and insulin-like growth-factors ( IGFs ) may contribute to breast cancer development . The present study analyzed the hypothesis that serum glucose , insulin levels , and IGF-I pattern are associated with breast cancer using a nested case-control study . Between 1987 and 1992 , 10,786 women ages 35 - 69 were recruited in a prospect i ve study in Italy . Women with history of cancer and on hormone therapy were excluded at baseline . At recruitment ,  blood sample s were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants . After 5.5 years , 144 breast cancer cases were identified among the participants of the cohort . Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period . In premenopausal women , glucose was associated with breast cancer risk : the age , body mass index , and reproductive variable adjusted relative risk ( RR ) for the highest quartile of serum glucose versus the lowest was 2.8 [ 95 % confidence interval ( CI ) , 1.2 - 6.5 ] , and P for trend was 0.02 . Insulin showed a weaker association with breast cancer , the adjusted RR of the highest quartile versus the lowest was 1.7 ( 95 % CI , 0.7 - 4.1 ) , and P for trend was 0.14 , whereas the adjusted RR of the highest quartile of IGF-I was 3.1 ( 95 % CI , 1.1 - 8.6 ) , and P for trend was 0.01 . Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk : the adjusted RR for the highest quartile was 2.1 ( 95 % CI , 0.95 - 4.75 ) , and P for trend was 0.02 . In postmenopausal women , the associations of glucose , insulin , and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26 . These results indicate that chronic alteration of glucose metabolism is related to breast cancer development Blood concentrations of insulin-like growth factor-I ( IGF-I ) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) have recently been associated with breast cancer risk , notably in women who developed breast cancer at a young age . Prospect i ve studies published so far , however , were relatively small and odds ratio ( OR ) estimates imprecise . We present the results of a large prospect i ve case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition on total IGF-I , IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects . Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age ( highest vs lowest quintile OR 1.38 ( 95 % confidence interval ( CI ) 1.02 - 1.86 ) , P = 0.01 , and 1.44 ( 95 % CI 1.04 - 1.98 ) , P = 0.01 , respectively ) , but no relationship was observed in younger women ( OR = 1.03 ( 95 % CI 0.60 - 1.77 ) , P = 0.81 for IGF-I , and OR = 0.92 ( 95 % CI 0.50 - 1.70 ) , P = 0.69 for IGFBP-3 ) . There was , however , significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis . A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation , ( OR = 0.76 ( 95 % CI 0.57 - 1.03 ) ) , while an increase in risk was observed for women with a later diagnosis ( above or equal to two years after blood collection , OR = 1.51 ( 95 % CI 1.19 - 1.91 ) ) . A similar pattern was observed for IGFBP-3 . This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk , particularly for women with a later diagnosis of cancer , but it does not support the hypothesis of an involvement of IGF-I in younger women BACKGROUND Insulin-like growth factor I ( IGF-I ) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor . The major binding protein for IGF-I , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor . In a prospect i ve study of men in Shanghai , China , we examined the association between serum levels of IGF-I and  IGFBP-3  and the subsequent risk of lung cancer . METHODS From 1986 to 1989 , serum was collected from 18,244 men aged 45 - 64 years living in Shanghai without a history of cancer . We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects . RESULTS Among 230 case patients and 659 matched control subjects , increased IGF-I levels were not associated with increased risk of lung cancer . However , for subjects in the highest quartile relative to the lowest quartile of IGFBP-3 , the odds ratio ( OR ) for lung cancer , adjusted for smoking and IGF-I , was 0.50 ( 95 % confidence interval [ CI ] = 0.25 to 1.02 ) . When the analysis was restricted to ever smokers ( 184 case patients and 344 matched control subjects ) , the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile , adjusted for smoking and IGF-I , was 0.41 ( 95 % CI = 0.18 to 0.92 ) . CONCLUSIONS In this prospect i ve study of Chinese men , higher serum levels of IGF-I did not increase the risk of lung cancer . However , subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer . This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity . The association of plasma IGF-I and IGF binding protein-3 ( IGFBP-3 ) with pancreatic cancer risk has been investigated in two small studies , with conflicting results . We conducted a nested case – control study within four large , prospect i ve cohorts to investigate whether prediagnostic plasma levels of IGF-I , IGF-II , and IGFBP-3 were associated with pancreatic cancer risk . Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression , with adjustment for other known pancreatic cancer risk factors . No association was observed between plasma levels of IGF-I , IGF-II , or IGFBP-3 and incident diagnosis of pancreatic cancer . Relative risks for the highest vs the lowest quartile of IGF-I , IGF-II , and IGFBP-3 were 0.94 ( 95 % confidence interval ( CI ) , 0.60–1.48 ) , 0.96 ( 95 % CI , 0.61–1.52 ) , and 1.21 ( 95 % CI , 0.75–1.92 ) , respectively . The relative risk for the molar ratio of IGF-I and IGFBP-3 , a surrogate measure for free IGF-I , was 0.84 ( 95 % CI , 0.54–1.31 ) . Additionally , no association was noted in stratified analyses or when requiring longer follow-up . In four prospect i ve cohorts , we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I , IGF-II , or IGFBP-3 BACKGROUND Insulin-like growth factor-I ( IGF-I ) is a potent mitogen for normal and neoplastic cells , whereas IGF-binding protein-3 ( IGFBP-3 ) inhibits cell growth in many experimental systems . Acromegalics , who have abnormally high levels of growth hormone and IGF-I , have higher rates of colorectal cancer . We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospect i ve case-control study nested in the Physicians ' Health Study . METHODS Plasma sample s were collected at baseline from 14916 men without diagnosed cancer .  IGF-I , IGF-II , and IGFBP-3  were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects . All P values are two-sided . RESULTS IGFBP-3 levels correlated with IGF-I levels ( r=.64 ) and with IGF-II levels ( r=.90 ) . After controlling for IGFBP-3 , age , smoking , body mass index ( weight in kg/[height in m]2 ) , and alcohol intake , men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile ( relative risk [RR]=2.51 ; 95 % confidence interval [CI]=1.15 - 5.46 ; P for trend = .02 ) . After controlling for IGF-I and other covariates , men with higher IGFBP-3 had a lower risk ( RR=0.28 ; 95 % CI=0.12 - 0.66 ; P for trend = .005 , comparing extreme quintiles ) . The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men . IGF-II was not associated with risk . CONCLUSIONS Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer Insulin-like growth factors ( IGFs ) may play a role in prostate growth , hyperplasia , and malignancy . High plasma IGF-I has been associated with increased prostate cancer risk . In a prospect i ve , cohort , case-control study in the Baltimore Longitudinal Study on Aging population , we examined  prostate volume  by magnetic resonance imaging , and prostate-specific antigen ( PSA ) , IGF-I , IGF-II , and IGF-binding protein-3 ( IGFBP-3 ) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases ( n = 72 ) or age-matched controls ( n = 127 ) and in 76 additional Baltimore Longitudinal Study on Aging men ( normal subjects ) with measured prostate volumes and no prostate cancer . We calculated adjusted odds ratios ( OR ) by logistic regression , relative risks for significant ORs , and receiver operator curves for prostate cancer , using serum measures alone and in combination . Adjusted ORs for the high vs. low tertile were : for IGF-I , 3.1 [ confidence interval ( CI ) , 1.1 - 
    Output:
    
Our meta- analysis provides comprehensive support for a role of circulation IGF-I and IGF-II in the etiology of CRC