Dataset Information

Relationship of SNP rs35767 in IGF-1 promoter region with susceptibility to colorectal cancer.

ABSTRACT: In vitro and animal experiments demonstrate that IGF-1 appears to play a role in the development and growth of colorectal cancer and the function of free IGF-1 protein is mediated by IGF-1R. The IGF-1R system plays a critical role in promoting the normal development of cells and malignant transformation via the phosphatidylinositol 3-kinase (PI3)/AKTA and mitogen-activated protein kinase (MAPK) pathways. Different variants of the promoter of IGF-1 are involved in the risk of suffering from various diseases. The current study examined the relationship between IGF-1 rs35767 polymorphism and the risk of colorectal cancer (CRC) in a population from China. The genotypes of rs35767 polymorphism of the promoter region of IGF-1 were examined in 734 subjects: 367 patients with CRC and 367 healthy individuals by PCR. LDL and TC levels in colorectal cancer patients were significantly higher than those in the healthy control group (P = 0.045 and 0.046, respectively). Compared with CC genotype carriers, people with the CT genotype had a 1.39-fold higher risk of CRC (OR = 1.399, 95% CI 1.029-1.901 P = 0.032). There was no association between genotypes of rs35767 and the risk of CRC, after stratification according to gender. The patients who carried the T allele tend to have poor tissue differentiation. SNP rs35767 polymorphism associated with IGF-1 levels may be associated with susceptibility to colorectal cancer. People with the CT genotype may have a higher risk of CRC, and the patients who carried T allele tend to have poor tissue differentiation.

SUBMITTER: Li Y

PROVIDER: S-EPMC6962907 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Relationship of SNP rs35767 in IGF-1 promoter region with susceptibility to colorectal cancer.

Li Yang Y Zhou Xiaojie X Liu Rui R Cao Yujie Y Wang Lele L Chao Xiangli X Zhang Sha S

International journal of clinical and experimental pathology 20181001 10

In vitro and animal experiments demonstrate that IGF-1 appears to play a role in the development and growth of colorectal cancer and the function of free IGF-1 protein is mediated by IGF-1R. The IGF-1R system plays a critical role in promoting the normal development of cells and malignant transformation via the phosphatidylinositol 3-kinase (PI3)/AKTA and mitogen-activated protein kinase (MAPK) pathways. Different variants of the promoter of IGF-1 are involved in the risk of suffering from vario ...[more]

PMID: 31949589

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Project description:BackgroundBreast cancer predisposition genes identified to date (e.g., BRCA1 and BRCA2) are responsible for less than 5% of all breast cancer cases. Many studies have shown that the cancer risks associated with individual commonly occurring single nucleotide polymorphisms (SNPs) are incremental. However, polygenic models suggest that multiple commonly occurring low to modestly penetrant SNPs of cancer related genes might have a greater effect on a disease when considered in combination.MethodsIn an attempt to identify the breast cancer risk conferred by SNP interactions, we have studied 19 SNPs from genes involved in major cancer related pathways. All SNPs were genotyped by TaqMan 5'nuclease assay. The association between the case-control status and each individual SNP, measured by the odds ratio and its corresponding 95% confidence interval, was estimated using unconditional logistic regression models. At the second stage, two-way interactions were investigated using multivariate logistic models. The robustness of the interactions, which were observed among SNPs with stronger functional evidence, was assessed using a bootstrap approach, and correction for multiple testing based on the false discovery rate (FDR) principle.ResultsNone of these SNPs contributed to breast cancer risk individually. However, we have demonstrated evidence for gene-gene (SNP-SNP) interaction among these SNPs, which were associated with increased breast cancer risk. Our study suggests cross talk between the SNPs of the DNA repair and immune system (XPD-[Lys751Gln] and IL10-[G(-1082)A]), cell cycle and estrogen metabolism (CCND1-[Pro241Pro] and COMT-[Met108/158Val]), cell cycle and DNA repair (BARD1-[Pro24Ser] and XPD-[Lys751Gln]), and within carcinogen metabolism (GSTP1-[Ile105Val] and COMT-[Met108/158Val]) pathways.ConclusionThe importance of these pathways and their communication in breast cancer predisposition has been emphasized previously, but their biological interactions through SNPs have not been described. The strategy used here has the potential to identify complex biological links among breast cancer genes and processes. This will provide novel biological information, which will ultimately improve breast cancer risk management.

Project description:The pathogenesis of colorectal cancer (CRC) is poorly understood. MicroRNA (miR)-32 upregulation in CRC tissues was previously reported, where it increased the proliferation, migration and invasion, and reduced apoptosis of CRC cells by inhibiting the expression of phosphatase and tensin homolog (PTEN). However, the mechanism underlying miR-32 upregulation remains unknown. miR-32 is an intronic miRNA located within intron 14 of the transmembrane protein 245 gene (TMEM245). The present study aimed to elucidate the biological pathways underlying miR-32 regulation in CRC. A truncated promoter containing the 5'-flanking region of TMEM245/miR-32 gene was constructed. The promoter region was analyzed by dual luciferase reporter assay in CRC cells. DNA pull-down assay and mass spectrometry (MS) were used to identify proteins binding to the core promoter. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and transcription factor (TF) analyses were used to identify the binding proteins. The -320 to -1 bp fragment of the 5'-flanking region exhibited the highest luciferase activity. The regions spanning -606 to -320 bp exhibited a significant decrease in luciferase activity, compared with the -320 to -1 bp fragment. DNA pull-down assay and MS revealed 403 potential miR-32 promoter binding proteins. GO and KEGG pathway analysis indicated that these proteins were involved in numerous physiological and biochemical processes, including 'structural molecule activity', 'RNA binding', 'small molecule metabolic process' and 'biogenesis'. Furthermore, TF analysis revealed 10 potential interacting TFs, including SMAD family member 1 (SMAD1), signal transducer and activator of transcription 1 (STAT1) and forkhead box K1 (Foxk1). These results suggested that the core promoter region may be located within-320 to -1 bp of the 5'-flanking region of TMEM245/miR-32 gene, while the region from -606 to -320 bp may harbor repressive regulatory elements. The TFs SMAD1, STAT1 and Foxk1 may be involved in the transcriptional regulation of miR-32.

Dataset Information

Relationship of SNP rs35767 in IGF-1 promoter region with susceptibility to colorectal cancer.

Publications

Relationship of SNP rs35767 in IGF-1 promoter region with susceptibility to colorectal cancer.

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