Genetic variations in the IGF-IGFR-IGFBP axis confer susceptibility to lung and esophageal cancer

Huang, Xin-En; Zhou, Wenwen; Zhang, Y.F.

doi:10.4238/2014.january.24.17

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…IGFBP-3 is able to bind to IGF-I and IGF-II and regulate the concentrations of these proteins in circulation; therefore, it has been demonstrated to inhibit cell proliferation, promote apoptosis and reduce growth in numerous types of solid tumor, including breast cancer and prostate cancer (25–28). In addition, IGFBP-3 has been reported to possess pro-apoptotic and anti-proliferative functions, via its interactions with other signaling receptors or proteins, to regulate cell apoptosis, cell proliferation and the bioavailability of insulin and IGFs (29). A previous study revealed that IGFBP-3 exerts no direct effect on Hs578T breast cancer cells, but is able enhance apoptosis induced by the physiological trigger ceramide in an IGF-independent manner (30).…”

Section: Discussionmentioning

confidence: 99%

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma

Yan

Yang

et al. 2017

Oncology Letters

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Abstract. Insulin-like growth factor binding protein-3 (IGFBP-3) has previously been identified as a putative tumor suppressor gene. The present study investigated the clinical and prognostic significance of IGFBP-3 expression levels in patients with hepatocellular carcinoma (HCC). Immunohistochemistry (IHC) probing for IGFBP-3 was performed on paraffin-embedded tissue samples obtained from 120 patients with HCC, including tissue samples from 120 primary cancer sites and 50 matched adjacent non-malignant sites. Receiver-operator curve (ROC) analysis was used to determine the cut-off scores for the presence of IGFBP-3-positive tumor cells and to estimate the survival time of the patients. The threshold for marking the positive expression of IGFBP-3 was 65%, based on the area under the ROC. Positive expression of IGFBP-3 was observed in 65/120 (54.2%) of the HCC tissues, and in 36/50 (72%) of the adjacent non-malignant liver tissues. Low levels of IGFBP-3 expression were correlated with tumor size (P=0.003), tumor multiplicity (P=0.044), node (P=0.008), metastasis (P=0.001) and clinical stage (P=0.001), as well as reduced survival time (P= 0.015). Using univariate survival analysis, a significant direct correlation between high and low IGFBP-3 expression levels, and patient survival time (mean survival time high IGFBP-3, 39.4 vs. low IGFBP-3, 18.7 months) was identified. Kaplan-Meier analysis demonstrated that IGFBP-3 expression levels and patients survival time were significantly correlated (P<0.001). Multivariate analysis revealed IGFBP-3 expression to be an independent parameter (P= 0.003). Therefore, low levels of IGFBP-3 expression are associated with advance clinicopathological classification and may be a predictor of poor survival in patients with HCC. Furthermore, these findings suggest that IGFBP-3 may serve as an independent molecular marker for the evaluation of prognosis in patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma

Yan

Yang

et al. 2017

Oncology Letters

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“…Thus, attained height may represent cumulative exposure to IGF-1 throughout important periods of growth and development (i.e., in utero, childhood, adolescence) [65]. High levels of IGF-1 have also been shown to be positively associated with colorectal, lung, and prostate cancers [66–68]. Other lifestyle risk factors for colorectal cancer, such as increased caloric intake [69], being overweight [70], and having a sedentary lifestyle [71], have demonstrated higher levels of IGF-1 via increased insulin production and subsequent inhibition of IGF-binding protein synthesis [70].…”

Section: Discussionmentioning

confidence: 99%

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

et al. 2016

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BackgroundObservational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers.Methods and FindingsA systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate.ConclusionsOur study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

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“…Lung is the most common site for secondary primary malignancies in patients with esophageal cancer [4]. Accumulating evidence indicates that lung and esophageal cancers share many common genetic variants, such as deletion of CASP and CYP2A6 gene [3, 6], SOX2 expression [2], IFGR -IGFBP axis [7] and WDHD1 [8], especially in an Asian population.…”

Section: Introductionmentioning

confidence: 99%

Shared susceptibility loci at 2q33 region for lung and esophageal cancers in high-incidence areas of esophageal cancer in northern China

et al. 2017

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BackgroundCancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population.MethodsA total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson’s Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival.ResultsFour of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107–1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100–1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098–1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089–1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with gender, TNM stage, histopathological type, smoking, family history and overall survival.ConclusionsThe present study identified four high-risk SNPs at 2q33 locus for Chinese lung cancer and demonstrated the shared susceptibility loci at 2q33 region for Chinese lung and esophageal cancers.

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Genetic variations in the IGF-IGFR-IGFBP axis confer susceptibility to lung and esophageal cancer

Cited by 10 publications

References 29 publications

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Shared susceptibility loci at 2q33 region for lung and esophageal cancers in high-incidence areas of esophageal cancer in northern China

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