Serum IGF-binding Protein-3 Levels Research Articles

P4-10-11: Genetic and Environmental Predictors, Endogenous Hormones and Growth Factors and Risk of Estrogen Receptor-Positive Breast Cancer in Japanese Women.

Abstract The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We have recently demonstrated that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype. It is necessary to establish risk factors capable of predicting the risk of ER-positive breast cancer which will enable the efficient selection of candidates for preventive chemotherapy. We analyzed genetic factors, including 14 single nucleotide polymorphisms (SNPs), environmental risk factors (body-mass index (BMI), age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) and mammographic density in 913 women with breast cancer and 278 disease-free controls. To identify important risk factors, risk prediction models for ER-positive breast cancer in both pre- and postmenopausal women were created by logistic regression analysis. In premenopausal women, 1 SNP (CYP19A1-rs10046), age, pregnancy, breastfeeding, alcohol intake, serum levels of prolactin, testosterone and IGFBP3 were considered to be risk predictors. In postmenopausal women, 1 SNP (TP53-rs1042522), age, BMI, age at menopause, serum levels of testosterone and IGF1 were identified as risk predictors. Risk factors may differ between women of different menopausal status, and inclusion of common genetic variants and serum hormone measurements as well as environmental factors might improve risk assessment models. Further validation studies will clarify appropriate risk groups for preventive chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-11.

Reference values for serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Korean children and adolescents

ObjectiveMeasurements of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) are utilized in the diagnostic work-up and clinical management of children with growth disorders. We designed this study to establish the reference values of serum IGF-I and IGFBP-3 levels according to age, sex and pubertal stage in Korean children and adolescents. MethodsFor the study, 1378 healthy Korean children and adolescents aged 0 to 17years (722 boys, 656 girls) were randomly selected. Blood samples were collected, and the stored sera were assayed for IGF-I and IGFBP-3 using immunoradiometric assay (IRMA, Immunotech). The R 2.8.1 program (Bell Laboratories) was used to generate reference percentile curves for IGF-I and IGFBP-3 according to age, sex, and pubertal stage ResultsSerum IGFBP-3 level was higher in girls compared to that in boys of the same ages throughout the pubertal period, whereas IGF-I was only higher for girls younger than 13years of age. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage, followed by a progressive decline thereafter. Peak levels of serum IGF-I and IGFBP-3 were observed two years earlier in girls compared to those in boys (13 vs. 15years of age, respectively). Serum IGF-I and IGFBP-3 concentrations were highest at Tanner stage IV in boys and girls, with a subsequent decline. ConclusionsOur reference value model based on age, sex, and pubertal stage can improve the diagnostic utility of IGF-1 and IGFBP-3 levels in the evaluation and management of Korean children and adolescents with growth disorders.

UP-01.024 The Association Between Bladder Cancer and a Single Nucleotide Polymorphism (Rs2854744) in the Insulin-Like Growth Factor (IGF) Binding Protein-3 (IGFBP-3) Gene

Insulin-like growth factors (IGF) regulate growth and development, and enhance cellular proliferation. IGF binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics.

UP-02.092 Relationship of Insulin-Like Growth Factor (IGF) Binding Protein-3 (IGFBP-3) Gene Polymorphism with the Susceptibility to Development of Prostate Cancer and Influence on Serum Levels of IGF-I, and IGFBP-3

The insulin-like growth factor (IGF) axis plays a critical role in both the normal and cancer cell growth. IGF-I binds to the IGF-I receptor and begins a signaling cascade that regulates cell proliferation, apoptosis, and differentiation. The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH).

Associations of Ionizing Radiation and Breast Cancer-Related Serum Hormone and Growth Factor Levels in Cancer-Free Female A-Bomb Survivors

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.

Serum IGF-1 and IGFBP-3 Levels in Healthy Children Between 0 and 6 Years of Age - Original Article

Objective: Along with growth hormone (GH) levels, measurements of serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) are used in the diagnosis of GH deficiency and in monitoring the efficacy and safety of long-term GH treatment. The purpose of the present study was to establish reference values for serum IGF-1 and IGFBP-3 in healthy Turkish children less than 6 years of age.Methods: This study was designed as a multicenter project. Five hundred sixty-seven healthy children younger than 6 years of age from different geographical regions of Turkey, with weight and height values between the 10th and 90th percentiles according to the national standards were included in the study. In addition to anthropometric parameters, serum IGF-1 and IGFBP-3 levels were measured in all subjects.Results: Although not statistically significant, the serum IGF-1 levels in infants at age 6 months were lower than those in infants at age 3 months. The IGF-1 levels showed a slow increase with age. Serum IGF-1 levels were lower in girls as compared to boys only at age 6 months. No correlation was found between either serum IGFBP-3 levels and body mass index (BMI) or serum IGFBP-3 and weight and height standard deviation scores (SDS). A weak correlation was observed between serum IGF-1 and IGFBP-3 concentrations.Conclusions: The age- and gender-specific reference values for serum IGF-1 and IGFBP-3 reported in this study will aid in the diagnosis of GH deficiency and in the monitoring of children receiving GH treatment.Conflict of interest:None declared.

Insulin-like growth factor (IGF)-I and IGF-binding protein-3 serum levels in relapsing-remitting and secondary progressive multiple sclerosis patients

Insulin-like growth factor (IGF)-I has a role in remyelination, and insulin-like growth factor-binding protein-3 (IGFBP-3) might reduce its bioavailability. A role of IGFBP-3 in multiple sclerosis (MS) progression was hypothesized in patients with primary progressive (PP) MS. To evaluate serum levels of IGF-I and IGFBP-3 in patients with relapsing-remitting (RR) and secondary progressive (SP) MS and their correlations with disease activity and progression. Sixty-three (41 RR and 22 SP) 'naive' MS patients and 60 age-matched healthy controls were enrolled. Patients were assessed through clinical [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), number of relapses] and laboratory investigations. IGF-I and IGFBP-3 were measured by ELISA. Levels of IGF-I and IGFBP-3 were similar in the two MS groups. IGFBP-3 levels were higher in patients with MS than in controls (P < 0.001), with a reduction in IGF-I/BP3 ratio (P < 0.001). Patients showing IGFBP-3 levels higher than 2SD of the normal population had a higher EDSS (mean EDSS 3.7 vs. 2.8, P = 0.021). MSSS was not related to IGF-I or IGFBP-3 serum levels. Our patients showed high IGFBP-3 serum levels respect to controls and higher serum levels were associated with a higher EDSS, despite of comparable disease duration. Therefore, MS and higher disability seem to be associated with a reduction in bioavailability of IGF-I. MSSS score was not related to IGFBP-3 levels, suggesting that IGFBP-3 might not have the pathogenetic role previously suggested for PP MS, in the mechanism of progression in the SP form of disease.

Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3

The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR–RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 −202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ2=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ2=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17–0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29–0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577ng/ml, 3929ng/ml and 3349ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH.

Preoperative insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) blood level predicts gleason sum upgrading

About 43% of men with low Gleason grade prostate cancer (PCa) at biopsy will be finally diagnosed with high-grade PCa at radical prostatectomy (RP). Gleason sum at RP is a good indicator of biochemical recurrence and poor clinical outcome. Therefore, there is a need to improve clinical evaluation of PCa aggressiveness in order to choice appropriate treatment. To this aim an easy-available tool is represented by circulating biomarkers. Among these, the best candidates are some molecules involved in PCa pathogenesis such as IGFBP-2 and IGFBP-3, IL-6, and its soluble receptor (SIL-6R). In this study, we evaluated the ability of preoperative IGFBP-2, IGFBP-3, IL-6, and SIL-6R serum levels to predict Gleason score upgrade in 52 PCa patients. We found that IGFBP-3 median levels were significantly lower in patients who showed Gleason upgrading from biopsy to RP (P = 0.024). We also found an association between biopsy T-stage and Gleason Upgrade (P = 0.011). Using multivariate logistic regression model, we demonstrated that the association of IGFBP-3 serum levels together with biopsy T-stage and biopsy Gleason score was useful to calculate a prognostic risk score. ROC curve analysis of risk score showed a good ability to predict GSU (AUC = 0.81; 95% CI 0.69-0.93). Our results suggest that preoperative IGFBP-3 circulating levels determination may be useful to predict Gleason score upgrading alone and/or in combination with biopsy T-stage and biopsy Gleason score.

Dietary Intervention of Flaxseed: Effect on Serum Levels of IGF-1, IGF-BP3, and C-Peptide

Higher levels of insulin and insulin-like growth factor 1 (IGF-1) increase cancer risk by stimulating cell proliferation and increasing survival of DNA-damaged cells through antiapoptotic mechanisms. Laboratory studies suggest that flaxseed added to the diet may lower circulating levels of insulin and IGF-1, but there is limited information on the effects of dietary flaxseed on these biomarkers of cancer risk in humans. The aim of this study was to determine the effect of flaxseed supplementation in postmenopausal women on serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGF-BP3), and C-peptide, a marker of insulin production. Forty-eight postmenopausal women participated in this 12-wk baseline to postintervention study. Participants were asked to consume 7.5 g per day of ground flaxseed for 6 wk and 15 g per day for an additional 6 wk. No significant changes were observed in blood levels of IGF-1, IGF-BP3, or C-peptide over the study intervention. Flaxseed supplementation did not impact circulating levels of IGF-1, IGF-BP3, or C-peptide. Longer duration of intake may be necessary to observe changes in these biomarkers of cancer risk.

The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics. One single nucleotide polymorphism (rs2854744) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) technique. One hundred and sixty-two bladder cancer patients were genotyped for this SNP. The genotypes were compared with those of a random sample of 324 age-matched controls of the general population. Serum levels of IGF-I and IGFBP-3 were also determined. We found statistically significant differences in the genotypic distribution between the cases and the control subject (χ(2)=6.43, df=2.0, P=0.028). Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 1.76 (95% CI: 1.27-2.84; P=0.038). We detected a significantly decreased risk of bladder cancer associated with the AA genotype (adjusted OR=0.48; 95% CI=0.24-0.64; P=0.001) compared with the CC genotype. This decreased risk was more pronounced for invasive bladder cancer. Age-adjusted mean serum IGFBP-3 levels were lowest in the individuals with the CC genotype. We found a positive correlation between age-adjusted serum IGFBP-3 levels and circulating IGF-1 concentrations (16% difference in IGFBP-3 in top vs. bottom tertiles of IGF-1, P for trend=0.001), which was comparable across genotypes at the -202 IGFBP-3 locus (interaction term, F=0.10, P=0.87). Genetic polymorphism of the IGFBP-3 gene may be involved in the etiology of bladder TCC, and our results need further confirmation by larger studies.

Yetişkin Sağlıklı Bir Türk Toplum Örnekleminde İnsülin-Benzeri Büyüme Faktörü-I ve IGF-Bağlayıcı Protein-3 Seviyeleri

Amaç: İnsülin benzeri büyüme faktörü-I (IGF-I) ve IGF-bağlayıcı protein-3 (IGFBP 3) seviyeleri büyüme hormonu (GH) ilişkili hastalıkların tanısında önemli belirteçlerdir. Normal IGF-I ve IGFBP- 3 seviyeleri farklı etnik gruplar arasında değişkenlik göstermektedir ve farklı populasyonlara göre belirlenenen referanslar bazı tanı, tedavi ve izlemde bazen yanlış yönlenmeye neden olabilmektedir. Biz bu amaçla sağlıklı yetişkin Türk toplum örnekleminde IGF-I ve IGFBP-3 düzeylerini inceledik. Gereç ve Yöntemler: Sekiz yüz otuz üç olgu (512 kadın, 321 erkek) çalışmaya alındı. Serum IGF-I ve IGFBP-3 seviyeleri tüm olgularda bir immünoradyometrik tetkikle ölçüldü. Çalışma populasyonu yaş grupları (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 yaş) ve cinsiyet gruplarına (<30 yaş populasyon kadın ve erkekler olarak ayrılırken >30 yaş grubunda birlikte) ayrıldı ve sonuçlar üretici firmanın referans bir toplumu temsil eden referans değerleri ile karşılaştırıldı. Bulgular: Serum IGF-I değerleri ≤30 yaştaki bütün kadın yaş gruplarında referans seviyelerinden istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Erkeklerde sadece 26-30 yaş arası grupta IGF-I seviyeleri istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Otuz yaş üstündeki cinsiyet yönünden birlikte ele alınan gruplarda IGF-I seviyeleri referans seviyelerinden istatistiksel olarak daha yüksekti (p< 0.05). Serum IGFBP-3 seviyeleri 24-25 yaş arası grupta her iki cinsiyette, 18-20 yaş arası grupta ise erkeklerde referans değerlerinden daha düşüktü (p< 0.05). Serum IGFBP-3 seviyeleri 26-30 yaş arası grupta erkeklerde ve >30 yaş üstünde cinsiyet yönünden birleşik gruplarda istatistiksel açıdan anlamlı derecede daha yüksekti (p< 0.05). Sonuç: Çalışma populasyonumuzdaki serum IGF-I konsantrasyonları ticari kitin referans değerlerinden genelde daha yüksekti. GH'la ilişkili bozukluklarla ilgilenen merkezlerin tanı ve izlemde olası hatalardan kaçınabilmek amacıyla kendi populasyonlarının normal IGF-I ve IGFBP-3 değerlerini belirlemeleri yararlı olabilecektir.

The effect of corrective surgery on serum IGF-1, IGFBP-3 levels and growth in children with congenital heart disease

The aim of this study is to evaluate growth and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in infants with congenital heart disease (CHD) pre- and postoperatively over a period of a year. Anthropometric values and serum levels of IGF-1 and IGFBP-3 of 40 infants with CHD (20 cyanotic and 20 acyanotic) were compared with 32 healthy controls. Acyanotic infants and infants with pulmonary hypertension (PH) presented significantly more growth failure. Preoperatively, serum IGF-1 and IGFBP-3 levels were lower in the acyanotic group than the cyanotic and the control groups (p = 0.22; p < 0.01). The upward trend in IGF-1 and IGFBP-3 levels in this year-long study demonstrated that the values in the third month and the first year were higher than the preoperative values (p < 0.05). The parallel increase of weight gain and IGF-1, IGFBP-3 levels were the best evidence that these parameters are good nutritional indicators. Timing the corrective surgery before chronic malnutrition or PH develops is an important issue to maintain a normal growth for children with CHD.

Evaluation of Growth Status Using Serum IGF-I and IGFBP-3 in Children with Subclinical Hypothyroidism

Purpose : The aim of this study was to evaluate growth status using the insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations in children with subclinical hypothyroidism (SCH). Methods : The study included 93 SCH patients (33 males and 60 females, age 8.1±1.9 years) and 94 healthy control subjects (31 males and 63 females, age 8.0±0.7 years). Patients’ height and weight were measured, and their body mass index (BMI) and Z-scores were calculated. The relationship between growth parameters, including IGF-I and IGFBP-3 concentrations and thyroid functions (thyroid-stimulating hormone (TSH) and free thyroxine 4 (fT4) was explored. Results : Although weight and BMI were greater in SCH patients, the Z-score of height, weight and BMI, and serum IGF-I and IGFBP-3 levels in SCH children were not significantly different compared to the control. In SCH patients, TSH showed a negative correlation with weight Z-scores (r =-0.23, P =0.028) and BMI Z-scores (r =-0.21, P =0.048). FT4 showed a positive correlation with IGFBP-3. Conclusion : The positive correlation of fT4 and IGFBP-3 and the negative relationship between TSH and weight and BMI Z-scores in SCH children suggest that subnormal thyroid functions could be related to growth impairment. (J Korean Soc Pediatr Endocrinol 2011;16:31-37)

Abstract PR-1: Genetic African ancestry and race differences in blood insulin-like growth factor 1 (IGF-1), IGF-2, and IGF binding protein 3 (IGFBP-3)

Abstract Purpose: We have previously reported that African American women have significantly higher IGF-1 levels, and lower IGF-2 and IGFBP-3, compared to white women. This investigation aims to determine if genetic African ancestry is associated with these racial differences in blood IGF levels. Methods: The Southern Community Cohort Study (SCCS) is a prospective cohort study of 86,000 men and women, with two-thirds African American recruitment, designed to investigate racial disparities in cancer. We randomly selected 1000 African American and 1000 non-Hispanic white female participants to support focused investigations of racial differences in biomarkers possibly related to breast cancer. Serum IGF-1, IGF-2, and IGFBP-3 levels were measured by ELISA. We estimated African and European admixture using a panel of 276 ancestry informative genetic markers. Final analyses included 821 African American women and 816 white women after excluding women taking hormone replacement therapy or insulin for diabetes. White women had a low African ancestry (median = 0.4%, range=0.1 % to 17.1 %) and thus were considered as a single ancestry category. For African Americans, cutpoints of &amp;lt;85% (n=149), 85%-95% (n=230), and ≥95% (n=442) defined “low,” “medium,” and “high” African ancestry. Using multivariable linear regression, we estimated differences in IGF levels across ancestry categories while adjusting for age, body mass index (BMI), height, menopausal status, and BMI at age 21 years. Results: African American women having 85% African ancestry. For example, IGF-2 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 1771.9 ng/ml, 1713.5 ng/ml, 1620.3 ng/ml, and 1620.6 ng/ml, respectively. African American women with &amp;lt; 85% African ancestry had IGF-2 levels that were about 5.8% higher than African American women with 85%-95% (p=0.03) or ≥95% (p=0.01) ancestry. IGF-1 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 134.7 ng/ml, 143.8 ng/ml, 147.8 ng/ml, and 147.4 ng/ml, respectively, while IGFBP-3 levels were 3871.8 ng/ml, 3816.9 ng/ml, 3629.0 ng/ml, and 3693.9 ng/ml, respectively. African American women with 85% African ancestry, but these differences in IGF-1 and IGFBP-3 levels between African American ancestry groups were not statistically significant. We also calculated the molar ratio of IGF-1 to IGFBP-3 as an index of biologically available or free IGF-1. Differences in free IGF-1 among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 0.126,0.137,0.148, and 0.145, respectively. Free IGF-1 levels were significantly lower among African American women with &amp;lt;85% compared to women with 85%-95% (p=0.02) or ≥95% (p=0.05) ancestry. Conclusion: Estimates of African ancestry are significantly associated with IGF-2 and free IGF-1, and suggest inherited genetic traits associated with African ancestry contribute to racial differences in IGF levels. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-1.

Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania

IGF1 mediates multiple physiological and pathophysiological responses in the cardiovascular system. The aim of this study was to analyze the association between serum IGF1 as well as IGF-binding protein 3 (IGFBP3) levels and endothelial function measured by flow-mediated dilation (FMD). Cross-sectional population-based observational study. The study population comprised 1482 subjects (736 women) aged 25-85 years from the Study of Health in Pomerania. Serum IGF1 and IGFBP3 levels were determined by chemiluminescence immunoassays. FMD measurements were performed using standardized ultrasound techniques. FMD values below the sex-specific median were considered low. In males, logistic regression analyses revealed an odds ratio (OR) of 1.27 (95% confidence interval (CI) 1.07-1.51; P=0.008) for decreased FMD for each decrement of IGF1 s.d. after adjustment for major cardiovascular confounders. In females, no significant relationship between serum IGF1 and FMD was found (OR 0.88, CI 0.74-1.05; P=0.147). After exclusion of subjects with the current use of antihypertensive medication, these findings were similar (males: OR 1.40, CI 1.12-1.75; P=0.003; females: OR 0.95, CI 0.77-1.16; P=0.595). There was no association between serum IGFBP3 levels and FMD in both sexes. Low serum IGF1 levels are associated with impaired endothelial function in males. In women, serum IGF1 is not associated with endothelial function.

Serum IGF-1 and IGFBP-3 levels in subclinical hypothyroid women

AbstractThyroid status is known to influence growth in mammals. The aim of this study is to investigate the possible relationship between autoimmune subclinical hypothyroidism and growth hormone (GH), insulin-like growth factor-1(IGF-1) and insulin-like growth factor binding protein-3(IGFBP-3) levels. Thirty-five women with autoimmune subclinical hypothyroidism, 33 years of age, were used as controls and enrolled in the study. Free triiodothyronin (FT3), free thyroxin(FT4), thyrotropin(TSH), anti-thyroid peroxidase(Anti-TPO), anti-thyroglobuline(Anti-Tg), GH, IGF-1 and IGFBP-3 levels were measured in blood samples and correlations among these parameters were evaluated. We found no significant differences in GH, IGF-1 or IGFBP-3 between patients and controls. In patients and controls, there were no correlations among thyroid hormones and IGF-1 or IGFBP-3 levels, but GH levels were correlated with FT3, FT4 and TSH only in patients’ group. In controls, only IGF-1 and IGFBP-3 levels were correlated. The present study suggests that subclinical hypothyroidism with high TSH and antibody status does not affect IGF-1 and IGFBP-3 levels in adult women. To our knowledge, this is the first study concerning the relationship between autoimmune subclinical hypothyroidism and IGF-1 and IGFBP-3 levels.

Lack of association between insulin-like growth factor-1 or insulin-like growth factor-binding protein-3 and left ventricular hypertrophy: results of the Study of Health in Pomerania

Left ventricular hypertrophy (LVH) is a major cardiac sequel of hypertension and a powerful predictor of cardiovascular morbidity and mortality. Several nonpopulation-based studies explored the association between insulin-like growth factor-1 (IGF-I) and LVH with conflicting results. The aim of the present study was to investigate the association of serum IGF-I or IGF-binding protein-3 (IGFBP-3) levels with LVH in a population-based study. From the cross-sectional Study of Health in Pomerania, 1865 participants aged 45-79 years were included. Echocardiography was performed and left ventricular mass index calculated. LVH was defined as left ventricular mass index more than 48 g/m for men and more than 44 g/m for women. Serum IGF-I and IGFBP-3 levels were determined by chemiluminescence immunoassays. Analysis of variance and logistic regression were performed. LVH was present in 52.0% of the women and 50.8% of the men. Our data did not obtain any significant association between serum IGF-I levels and left ventricular mass index or LVH in both men and women. Regarding IGFBP-3, women with low IGFBP-3 levels had an almost two-fold higher odds of LVH [odds ratio 1.76 (95% confidence limit 1.04-2.95)] compared with women with moderate IGFBP-3 levels. No such relation became apparent in men. No association between IGF-I levels and LVH was found. Potential hypertrophic effects of free serum IGF-I levels might be mediated by lower IGFBP-3 levels.

Influence of IGFBP3 Gene Polymorphisms on IGFBP3 Serum Levels and the Risk of Prostate Cancer in Low-risk Korean Men

To understand the relationship between the -202 A/C single-nucleotide polymorphism (SNP) of the insulin-like growth factor-binding protein 3 (IGFBP3) gene, IGFBP3 serum levels, and risk of prostate cancer (PCa) in a Korean population, as a potential reason for the lower incidence of PCa in the Korean population. The IGFBP3 levels were measured and the -202 A/C SNP of the IGFBP3 gene was typed for 225 PCa cases and the same number of matched controls. Linear regression analysis and unconditional logistic regression analysis were used to test for the associations between the genotypes and the circulating IGFBP3 levels and the risk of PCa, respectively. To adjust for the potential bias introduced by the hospital cohort, the result of the genotyping was compared with that of 683 community-indwelling healthy men. Significantly lower plasma levels of IGFBP3 were noted in the PCa cases. Lower IGFBP3 plasma levels were associated with an increased number of C alleles (P<.001). Compared with the PCa cases, a lower frequency of the C allele was found in the hospital and community controls (P<.05). Compared with AA genotype, logistic regression analysis revealed an increased risk of PCa in subjects who were CC genotype (odds ratio: 2.39, 95% confidence interval: 1.05-5.48). Larger odds (odds ratio: 3.37, 95% confidence interval: 1.35-8.43) for PCa were associated with CC genotype when the analysis was confined to those who had high-risk PCa. The results supported the protective role of -202 A/C SNP of the IGFBP3 gene against PCa in Korean men.

Changes in serum IGF-1 and IGFBP-3 levels and growth in children following adenoidectomy, tonsillectomy or adenotonsillectomy

Objective The aim of this study is to determine the effect of adenoidectomy, tonsillectomy or adenotonsillectomy on growth. For this purpose, we prospectively reviewed the postoperative changes in serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), weight and height in children that underwent adenoidectomy, tonsillectomy or adenotonsillectomy. Methods Ninety-six children with symptoms of sleep disordered breathing (SDB) or recurrent adenotonsillitis were enrolled to study. Blood samples were taken preoperatively and repeated at 6 months following operation to determine the changes in serum IGF-1 and IGFBP-3 levels, pre- and postoperative values of weight and height were recorded for each operation. Results Thirty-six patients underwent adenoidectomy, 52 patients underwent adenotonsillectomy and 8 patients underwent tonsillectomy. Seventy of the operations were performed for SDB and 26 were performed for recurrent adenotonsillitis. The mean serum levels of IGF-1 increased by 26%, from 126.74 ± 112.13 ng/ml to 159.82 ± 122.91 ng/ml ( p < 0.001) and IGFBP-3 levels increased by 7%, from 3.34 ± 1.17 μg/l to 3.57 ± 1.16 μg/l ( p < 0.05) 6 months after operation. The increase was independent from the preoperative diagnosis. There was a significant increase both in patients with SDB and in children with recurrent infections ( p < 0.001 for IGF-1, p < 0.05 for IGFBP-3). Their Z scores (standard deviation scores) for body weights (mean Z score from −0.06 ± 0.98 to 0.118 ± 1.18, p < 0.001) and heights (mean Z score from 0.30 ± 0.98 to 0.42 ± 0.88, p < 0.001) were significantly higher 6 months after the operation compared to preoperative period. Conclusions We found a significant increase in weight, height, and IGF-1 and IGFBP-3 levels of children with SDB or recurrent infections postoperatively. These results suggest that upper airway obstruction may not be the only mechanism that causes retardation on growth in children.