scholarly journals Plasma Biomarkers of Insulin and the Insulin-like Growth Factor Axis, and Risk of Colorectal Adenoma and Serrated Polyp

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Dong Hang ◽  
Xiaosheng He ◽  
Ane Sørlie Kværner ◽  
Andrew T Chan ◽  
Kana Wu ◽  
...  

Abstract Background Hyperinsulinemia, high insulin-like growth factor 1 (IGF1) levels, and low IGF binding protein 1 (IGFBP1) levels have been implicated in the relationship between obesity and increased risk of colorectal cancer (CRC). However, it remains inconclusive whether circulating biomarkers of insulin and the IGF axis are associated with conventional adenoma and serrated polyp, the two distinct groups of CRC precursors. Methods We prospectively examined the associations of plasma C-peptide, IGF1, IGFBP1, IGFBP3, and IGF1 to IGFBP3 ratio with conventional adenoma and serrated polyp among 11 072 women from the Nurses’ Health Studies. Multivariable logistic regression was used to calculate the odds ratio (OR) per 1-SD increase in each biomarker for overall risk of conventional adenoma and serrated polyp and according to polyp feature. Results During 20 years of follow-up, we documented 1234 conventional adenomas and 914 serrated polyps. After adjusting for various lifestyle factors (including body mass index), higher concentrations of IGFBP1 were associated with lower risk of serrated polyp (OR = 0.84, 95% confidence interval = 0.75 to 0.95, P = .005). The association was particularly strong for large serrated polyp (≥10 mm) located in the distal colon and rectum (OR = 0.59, 95% confidence interval = 0.39 to 0.87, P = .01). In contrast, we did not find any statistically significant association between the biomarkers and conventional adenoma. Conclusions A higher plasma level of IGFBP1 was associated with lower risk of serrated polyp. Our findings support a potential role of IGFBP1 in the serrated pathway of CRC in women.

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Hamidreza Saber ◽  
Jayandra J Himali ◽  
Alexa Beiser ◽  
Ashkan Shoamanesh ◽  
Alexandra Pikula ◽  
...  

Background: Insulin-like growth factor 1 (IGF-1), reduces progression of atherosclerosis and in cross-sectional studies low circulating IGF-1 is associated with increased carotid intima-media thickness. Yet, prospective data linking IGF-1 levels to development of stroke remain sparse and inconsistent. We related circulating IGF-1 levels to risk of incident stroke in a community-dwelling sample. Methods: Serum IGF-1 levels were assayed in 757 stroke-free participants (age 79+5 years, 62% women) from the Framingham original cohort (1990-1994), and related to prospectively ascertained, incident all-stroke and ischemic stroke using Cox models. Results: During a mean follow-up of 10.2 years in 757 participants, 119 developed stroke including 99 with ischemic stroke. After adjustment for age and sex, higher log-IGF1 levels were associated with a lower risk of incident ischemic stroke [hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.63- 0.99, p=0.043]. There was a threshold effect with subjects in the lowest quintile of IGF-1 levels having 2.56-fold higher risk of incident ischemic stroke (95% CI: 1.20, 5.45, p=0.015) compared to all others. We observed significant interaction between diabetes and IGF1 in their relation to ischemic stroke (p=0.016). In pre-specified subgroup analyses the effect was restricted to persons with diabetes and central obesity (waist-to-hip ratio in top quartile) in whom each SD increase in IGF-1 was associated with a 61% (HR: 0.39, 95%CI: 0.20-0.78, p=0.007), and 41% (HR: 0.59, 95%CI: 0.37- 0.95, p=0.031) lower risk of incident ischemic stroke, respectively. Results were similar for all-stroke. Conclusions: IGF-1 may have a protective role in the pathogenesis of ischemic stroke among persons with insulin resistance as manifested by diabetes and/or obesity.


2016 ◽  
Vol 38 (2) ◽  
pp. 589-597 ◽  
Author(s):  
Yiyang Li ◽  
Yang Li ◽  
Jialing Zhang ◽  
Changjun Zheng ◽  
He Zhu ◽  
...  

Background/Aims: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. Methods: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. Results: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta-analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). Conclusion: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jack C. M. Ng ◽  
C. Mary Schooling

Background: Basal metabolic rate is associated with cancer, but these observations are open to confounding. Limited evidence from Mendelian randomization studies exists, with inconclusive results. Moreover, whether basal metabolic rate has a similar role in cancer for men and women independent of insulin-like growth factor 1 increasing cancer risk has not been investigated.Methods: We conducted a two-sample Mendelian randomization study using summary data from the UK Biobank to estimate the causal effect of basal metabolic rate on cancer. Overall and sex-specific analysis and multiple sensitivity analyses were performed including multivariable Mendelian randomization to control for insulin-like growth factor 1.Results: We obtained 782 genetic variants strongly (p-value < 5 × 10–8) and independently (r2 < 0.01) predicting basal metabolic rate. Genetically predicted higher basal metabolic rate was associated with an increase in cancer risk overall (odds ratio, 1.06; 95% confidence interval, 1.02–1.10) with similar estimates by sex (odds ratio for men, 1.07; 95% confidence interval, 1.002–1.14; odds ratio for women, 1.06; 95% confidence interval, 0.995–1.12). Sensitivity analyses including adjustment for insulin-like growth factor 1 showed directionally consistent results.Conclusion: Higher basal metabolic rate might increase cancer risk. Basal metabolic rate as a potential modifiable target of cancer prevention warrants further study.


1994 ◽  
Vol 3 (Supple4) ◽  
pp. 183-186 ◽  
Author(s):  
Atsushi Murata ◽  
Yasuyuki Kobayashi ◽  
Toshiyuki Yasuda ◽  
Yukihiro Hasegawa ◽  
Masanori Minagawa ◽  
...  

2020 ◽  
Author(s):  
Danylo Rafhael Costa-Silva ◽  
Francisco Adelton Alves-Ribeiro ◽  
Maria da Conceição Barros-Oliveira ◽  
Larysse Cardoso Campos-Verdes ◽  
Renato de Oliveira Pereira ◽  
...  

Abstract Background: Breast cancer, the leading cause of cancer death among women worldwide, one of the major risk factors for breast cancer is genetic changes. Changes in the expression levels of the insulin-like growth factor 1 (IGF-1) gene have been associated with increased risk and aggressiveness of breast cancer. The IGF-1 gene encodes the IGF-1 peptide that is present in most human tissues, as in the normal and neoplastic mammary gland. Here, we conducted a systematic review to investigate the influence of IGF-1 gene expression levels in women with breast cancer.Methods: PubMed, Scopus, and Web of Science databases were searched for relevant studies published between February 2 and May 15, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find association between IGF-1gene expression and breast cancer.Results: A growing number of studies in women with breast cancer support, with controversial results, the influence of IGF-1 gene expression levels on clinical-pathological factors, disease-free survival, overall survival, and resistance to tamoxifen.Conclusions: Therefore, the elucidation of IGF-1 gene expression patterns through further studies may enable the characterization of women at high risk for breast cancer, as well as the development of effective prognostic and therapeutic strategies.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5945 ◽  
Author(s):  
Courtnay L. Baskerville ◽  
Subu Chockalingham ◽  
Patricia A. Harris ◽  
Simon R. Bailey

Background In horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at a lower affinity than IGF-1. Methods Immunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor antibody. In further studies, lamellar epithelial cells were obtained by collagenase digestion from the hooves of 18 normal horses, also euthanised for non-research purposes, and incubated for 48 h in the presence of insulin (0–2,000 m IU/ml). The increase in cell numbers was determined using a cell proliferation assay, and compared to the effect of zero insulin using one-way ANOVA. Results Immunohistochemistry demonstrated IGF-1 receptors on lamellar epidermal epithelial cells. With cultured cells, insulin caused a concentration-dependent increase in cell proliferation compared to untreated cells (maximal effect 63.3 ± 12.8% more cells after 48 h with 1,000 m IU/ml insulin; P < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor significantly inhibited the proliferative effect of insulin (P < 0.01). Discussion These results demonstrate that IGF-1 receptors are present on lamellar epithelial cells. At high physiological concentrations, insulin may activate these cells, by a mechanism involving IGF-1 receptors, resulting in a proliferative effect. This mechanism could help to explain the link between hyperinsulinemia and laminitis.


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