***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: 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 We investigated the acute ( 4 - 5 h ) and short-term ( 5 days ) effects of GH treatment on hepatic messenger RNA ( mRNA ) levels of the genes for the insulin-like growth factors ( IGFs ) , insulin-like growth factor binding protein-1 , -2 , and -3 ( IGFBPs ) , and the acid labile subunit ( ALS ) , as well as serum levels of these proteins in humans . At the mRNA level , we observed an increase in IGF-1 transcription ( + 173 % ) following GH treatment in the acute group , which remained elevated in the short-term treatment group . IGFBP-2 mRNA decreased after short-term GH treatment , without changes in IGFBP-1 or -3 expression . The ALS transcript level increased after 5 days . In serum , we found increased levels of IGF-I and insulin , and decreased levels of IGF-II , in the short-term treatment group . IGFBP-1 decreased in both treatment groups , whereas IGFBP-2 was reduced after 5 days treatment . ALS increased in the short-term group . We observed increased IGFBP-3 serum levels after 5 days of GH treatment , likely due to increased formation of the ternary complex . Our results show that the metabolic effects by GH on the IGF axis are complex . In addition to a direct stimulation of IGF-I and ALS expression , GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner , possibly facilitating enhanced IGF bioavailability to target tissues 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 BACKGROUND Insulin-like growth factor (IGF)-I , a mitogenic and antiapoptotic peptide , can affect the proliferation of breast epithelial cells , and is thought to have a role in breast cancer . We hypothesised that high circulating IGF-I concentrations would be associated with an increased risk of breast cancer . METHODS We carried out a nested case-control study within the prospect i ve Nurses ' Health Study cohort .  Plasma concentrations of IGF-I and IGF binding protein 3 ( IGFBP-3 )  were measured in blood sample s collected in 1989 - 90 . We identified 397 women who had a diagnosis of breast cancer after this date and 620 age-matched controls .  IGF-I concentrations were compared by logistic regression with adjustment for other breast-cancer risk factors . FINDINGS There was no association between IGF-I concentrations and breast-cancer risk among the whole study group . In postmenopausal women there was no association between IGF-I concentrations and breast-cancer risk ( top vs bottom quintile of IGF-I , relative risk 0.85 [ 95 % CI 0.53 - 1.39 ] ) . The relative risk of breast cancer among premenopausal women by IGF-I concentration ( top vs bottom tertile ) was 2.33 ( 1.06 - 5.16 ; p for trend 0.08 ) . Among premenopausal women less than 50 years old at the time of blood collection , the relative risk was 4.58 ( 1.75 - 12.0 ; p for trend 0.02 ) . After further adjustment for plasma IGFBP-3 concentrations these relative risks were 2.88 and 7.28 , respectively . INTERPRETATION A positive relation between circulating IGF-I concentration and risk of breast cancer was found among premenopausal but not postmenopausal women . Plasma IGF-I concentrations may be useful in the identification of women at high risk of breast cancer and in the development of risk reduction strategies . Additional larger studies of this association among premenopausal women are needed to provide more precise estimates of effect BACKGROUND Insulin-like growth factors ( IGFs ) , in particular IGF-I and IGF-II , strongly stimulate the proliferation of a variety of cancer cells , including those from lung cancer . To examine the possible causal role of IGFs in lung cancer development , we compared plasma levels of IGF-I , IGF-II , and an IGF-binding protein ( IGFBP-3 ) in patients with newly diagnosed lung cancer and in control subjects . METHODS From an ongoing hospital-based , case-control study , we selected 204 consecutive patients with histologically confirmed , primary lung cancer and 218 control subjects who were matched to the case patients by age , sex , race , and smoking status .  IGF-I , IGF-II , and IGFBP-3 plasma levels were measured by enzyme-linked immunosorbent assay and then divided into quartiles , based on their distribution in the control subjects . Associations between the IGF variables and lung cancer risk were estimated by use of odds ratios ( ORs ) . Reported P values are two-sided . RESULTS IGF and IGFBP-3 levels were positively correlated ( all r>.27 ; all P<.001 ) . High plasma levels of IGF-I were associated with an increased risk of lung cancer ( OR = 2.06 ; 95 % confidence interval [ CI ] = 1.19 - 3.56 ; P = .01 ) , and this association was dose dependent in both univariate and multivariate analyses . Plasma IGFBP-3 showed no association with lung cancer risk unless adjusted for IGF-I level ; when both of these variables were analyzed together , high plasma levels of IGFBP-3 were associated with reduced risk of lung cancer ( OR = 0.48 ; 95 % CI = 0.25 - 0.92 ; P = .03 ) . IGF-II was not associated with lung cancer risk . CONCLUSIONS Plasma levels of IGF-I are higher and plasma levels of IGFBP-3 are lower in patients with lung cancer than in control subjects . If these findings can be confirmed in prospect i ve studies , measuring levels of IGF-I and IGFBP-3 in blood may prove useful in assessing lung cancer risk Recent prospect i ve studies have suggested that insulin-like growth factor (IGF)-I levels are related to risk of some epithelial cancers . We previously reported in a case-control study a significant association between IGF-I level and lung cancer risk , with a 2-fold increased risk in the highest quartile . We now report the results of a lung cancer case-control study nested in the placebo arm of the beta-Carotene and Retinol Efficacy Trial in heavy smokers . We identified 159 cases for whom sera had been collected at least 3 years before diagnosis and for whom 2 suitable controls/case ( final number , 297 ) could be matched from the same study arm on age ( within 5-year intervals ) , sex , ethnicity , year of enrollment into the beta-Carotene and Retinol Efficacy Trial , year of blood draw , and exposure category ( smoking or asbestos ) . The cases were significantly heavier smokers than the controls ( mean pack-years , 58.7 and 45.9 , respectively ; P < 0.001 ) . An inverse relationship between IGF-I level and age was evident only for former smokers , and not for those who were current smokers at the time of blood draw . Both IGF-I and IGF-binding protein (IGFBP)-3 levels were higher in cases than in controls , but none of the differences achieved statistical significance . The odds ratios for IGF-I were around unity , except for subsets of heaviest smokers and those who had quit smoking for the longest period of time , in whom there were elevated risks in the second to fourth quartiles of IGF-I relative to the first quartile ( odds ratios , 2.21 - 2.91 ) , although again , none achieved statistical significance . For younger subjects , IGF-I was inversely associated with lung cancer risk in the models that also controlled for IGFBP-3 . Elevated risks for lung cancer were noted in the highest quartile of IGFBP-3 level , and these tended to be higher in current smokers and more recent quitters . These results do not support the conclusions of our prior case-control study . It is possible that current smoking or recent cessation may exert a suppressive effect on IGF-I levels ( notably in younger subjects with higher baseline levels ) that may obscure a relatively modest association between IGF-I level and lung cancer risk . On the other h and , risks associated with elevated IGFBP-3 level tended to be higher in current smokers and more recent quitters . This trend toward a positive association with IGFBP-3 level is unexpected and requires further investigation . Finally , from these data , we can not exclude the possibility that risk of lung cancer in nonsmokers may be related to IGF-I levels 
    Output:
    
Conclusion The association between circulating IGF- I levels and the risk of lung cancer were not statistically significant ; IGFBP-3 , acts as a tumor suppressor and has a inverse correlation with the risk of lung cancer