BackgroundEsophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide. The interaction of environmental risk factors and genetic factors might contribute to the carcinogenesis of EC synergistically.ResultsAll seven single locus polymorphisms of ALDH3B2 were not associated with risk of ESCC as evaluated by allelic, dominant, co-dominant, recessive and Cochran-Armitage trend tests. Stratified analyses showed these SNPs were not correlated with the susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. None of the major haplotypes were related with ESCC susceptibility.Materials and MethodsWe conducted a hospital-based case–control study to evaluate the combined effects of environmental risk factors and the single nucleotide polymorphisms (SNPs) of ALDH3B2 gene on the development of esophageal squamous carcinoma (ESCC). A total of 1043 ESCC cases and 1315 controls were recruited for this study. Seven ALDH3B2 SNPs and four environmental factors were selected as independent variables. ALDH3B2 SNPs were determined by ligation detection reaction method.ConclusionsOur study suggested that ALDH3B2 rs34589365, rs3741172, rs4646823, rs78402723, rs7947978, rs866907 and rs9787887 polymorphisms were not implicated with altered susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. Yet this conclusion needs to be verified in larger studies among different ethnic populations with validation design, the biological function of these SNPs in carcinogenesis are subject to further investigation.
Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in the carcinogenesis of esophageal squamous cell carcinoma (ESCC). We conducted a hospital-based case-control study to evaluate ten NAT2 tagging single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction method. In the single locus analyses, there was a borderline statistically significant difference in genotype frequencies of NAT2 rs1565684 T>C SNP between the cases and the controls (p = 0.057). The NAT2 rs1565684 CC genotype was associated with a borderline significantly increased risk for ESCC (CC vs. TT: adjusted OR = 1.77, 95% CI = 0.97–3.21, p = 0.063 and CC vs. TT/TC: adjusted OR = 1.68, 95% CI = 0.93–3.04, p = 0.085). The association was evident among older patients and patients who never drunk. After the Bonferroni correction, in all comparison models, NAT2 rs1565684 T>C SNP was not associated with ESCC risk (p>0.05). For the other nine NAT2 SNPs, after Bonferroni correction, in all comparison models, the nine SNPs were also not associated with ESCC risk (p>0.05). Thus, nine NAT2 tagging SNPs were not associated with risk of ESCC. NAT2 rs1565684 T>C SNP might play a slight role in ESCC etiology. Additional, larger studies and tissue-specific biological characterization are required to confirm the current findings.
Vitamin D receptor (VDR) gene polymorphisms have been reported to increase susceptibility to some malignant tumors, yet the effect on gastric cardiac adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital-based case-control study to examine the correlation of single nucleotide polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608 controls were enrolled in the study. Using ligation detection reaction, we found that the variant alleles of the four polymorphisms were not associated with risk of gastric cardiac adenocarcinoma. Further stratified analyses showed that there was an increased risk associated with VDR rs1989969 polymorphism among patients who were drinking or aged <60. The haplotypes VDR Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis of gastric cardiac adenocarcinoma, especially increased the risk in the younger and alcohol drinking Chinese population.
BackgroundEsophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC.MethodsWe conducted a hospital based case-control study to evaluate the genetic susceptibility of SNPs on the development of EC. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. Seven PADI4 SNPs were determined by ligation detection reaction method.ResultsOur findings suggested that the PADI4 rs2240337 GA/AA variants were significantly associated with decreased risk of ESCC. Haplotype PADI4 Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562 polymorphism was correlated with decreased susceptibility to ESCC, while Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was correlated with increased susceptibility of ESCC. Stratification analyses demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366 AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype. Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT, rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years), rs11203366 AA genotype was associated with increased risk of ESCC. PADI4 rs1886302 CC variant was associated with ESCC susceptibility in female cohort.ConclusionsOur study suggested that PADI4 rs2240337 G>A polymorphism may be correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered susceptibility of ESCC based on sex, age, smoking status and alcohol consumption. However, larger studies among different ethnic populations and further experiments using genetically mutated cells or animals are warranted to verify our conclusion.
Background Esophageal squamous cell carcinoma (ESCC) remains a significant public health concern worldwide due to its high incidence and mortality rates. Consequently, developing a robust predictive risk model centered on RNA expression and identifying novel target genes in ESCC is paramount. While previous studies have implicated DOCK9 in tumor prognosis, its specific role in ESCC remains to be elucidated. This study aims to investigate the prognostic significance of DOCK9 and its biological functions in ESCC. Methods We reanalyzed RNA microarray datasets (GSE67269, GSE20347, GSE53625) from the Gene Expression Omnibus (GEO) database to identify potential survival-associated genes and assess their expression in ESCC. We also comprehensively analyzed single-cell RNA sequencing (scRNA-seq) data from GSE160269, GSE188990, and The Cancer Genome Atlas (TCGA) ESCC cohorts to explore potential molecular mechanisms. Kaplan-Meier analysis determined the correlation between DOCK9/CD31 and prognosis. Protein expression of DOCK9 in ESCC tissues was examined through immunohistochemistry and Western blot analyses in a small cohort of six ESCC patients. The co-expression of DOCK9 and CD31 was verified using Immunofluorescence (IF) analysis. Additionally, we investigated the functional impact of DOCK9 on human umbilical vein endothelial cells (HUVECs) proliferation, migration, and tube formation using cell counting kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) staining assay, wound-healing assay, and tube formation assay. Results Our study identified 21 genes from GSE67269, GSE20347, and GSE53625 datasets based on differential and univariate COX analyses, enabling us to construct a prognostic risk model for ESCC where DOCK9 plays a central role. DOCK9 expression was markedly lower in cancerous tissues than in ESCC patients' paracancerous tissues. Furthermore, DOCK9 emerged as a survival-related risk factor in ESCC, exhibiting high expression in tumo endothelial cells (TECs) and playing a role in angiogenesis and tumor-associated fibroblasts development. Our immunity analysis suggested that DOCK9 might influence the immune landscape, and the DOCK9/CD31 ratio could serve as an indicator for assessing the response to immunotherapy in ESCC. Functionally, our assays indicated that inhibiting DOCK9 expression curtailed the proliferation, migration, and tube formation of ANG-2-stimulated HUVECs, a process potentially related to the ANG-2/Tie2 axis. Conclusions Our study provides evidence that DOCK9 could serve as a potential prognostic biomarker associated with angiogenesis and immune therapy in esophageal squamous cell carcinoma, thereby opening avenues for improved therapeutic strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.