Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma

Chang, Jiang; Zhong, Rong; Tian, Jianbo; Li, Jiaoyuan; Zhai, Kan; Ke, Juntao; Lou, Jiao; Chen, Wei; Zhu, Beibei; Shen, Na; Zhang, Yi; Zhu, Ying; Gong, Yajie; Yang, Yang; Zou, Detang; Peng, Xiaobo; Zhang, Zhi; Zhang, Xuemei; Huang, Kun; Wu, Tangchun; Wu, Chen; Lin, Dongxin

doi:10.1038/s41588-018-0045-8

Cited by 80 publications

(64 citation statements)

References 64 publications

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“…Moreover, an exome-wide analysis identified a variant (rs138478634) in CYP26B1 associated with esophageal squamous cell carcinoma. This SNP can modify the enzymatic activity of CYP26B1 32 . Functional analysis was not performed for the significant SNPs in the current study.…”

Section: Discussionmentioning

confidence: 94%

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

Zhu

Jia

et al. 2018

Molecular Therapy - Nucleic Acids

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Nucleotide excision repair (NER) is an essential mechanism of the body to defend against exogenous carcinogen-induced DNA damage. Defects in NER may impair DNA repair capacity and, therefore, increase genome instability and cancer susceptibility. To explore genetic predispositions to Wilms tumor, we conducted a case-control study totaling 145 neuroblastoma cases and 531 healthy controls. We systematically selected 19 potentially functional SNPs in six key genes within the NER pathway (ERCC1, XPA, XPC, XPD, XPF, and XPG). The odds ratio (OR) and 95% confidence interval (CI) were calculated to measure the strength of associations. We identified significant associations between two XPD SNPs and Wilms tumor risk. The XPD rs3810366 polymorphism significantly enhanced Wilms tumor risk (dominant model: adjusted OR = 2.12, 95% CI = 1.26–3.57). Likewise, XPD rs238406 conferred a significantly increased risk for the disease (dominant model: adjusted OR = 2.30, 95% CI = 1.40–3.80; recessive model: adjusted OR = 1.64, 95% CI = 1.11–2.44). Moreover, online expression quantitative trait locus (eQTL) analysis demonstrated that these two polymorphisms significantly affected XPD gene expression in transformed fibroblast cells. Our study provides evidence of the association between the two XPD polymorphisms and Wilms tumor risk. However, these findings warrant validation in larger studies.

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Section: Discussionmentioning

confidence: 94%

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

Zhu

Jia

et al. 2018

Molecular Therapy - Nucleic Acids

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“…There were 81 SNPs located in the noncoding region and among them, we found only two SNPs marked by the enhancer or promoter histone modification and showing significant eQTL with TNXB expression from the GTEx database with P < .01 in the esophageal mucosa tissues. These two SNPs also passed the P value threshold ( P < 1 × 10 −5 ) in our previous exome‐wide interrogation 11 . One of them was located in the 5′UTR of FKBPL gene and we excluded it in the subsequent analyses (Figure 4).…”

Section: Resultsmentioning

confidence: 96%

“…At the beginning, we included all variants that were in LD ( r 2 ≥ .2) with the tag SNP, rs204900, in our previous study 11 in the ASN population. We used HaploReg 34 (http://compbio.mit.edu/HaploReg) annotation and The Genotype‐Tissue Expression (GTEx) 35 (http://gtexportal.org) data to search for the potential regulatory SNPs.…”

Section: Methodsmentioning

confidence: 99%

“…Genome‐wide association studies (GWAS) have become a powerful tool to uncover genetic susceptibility factors for complex traits and diseases. To date, more than 20 ESCC GWAS risk loci have been identified 9‐13 . The vast majority of disease‐associated SNPs reside outside of protein‐coding regions 14‐16 and exert their roles by regulating the expression of their target genes 17–19 …”

Section: Introductionmentioning

confidence: 99%

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A functional variant in TNXB promoter associates with the risk of esophageal squamous‐cell carcinoma

Yang

Tian

Wang

et al. 2020

Molecular Carcinogenesis

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Our previous study identified a tag single‐nucleotide polymorphism (SNP) rs204900 in TNXB associated with risk of esophageal squamous‐cell carcinoma (ESCC) in the Chinese population. However, the functional role of TNXB and causal variants had not been interrogated in that study. In the present study, we explored the effects of TNXB expression in the development of ESCC and searched for functional variants in this gene. We found TNXB was downregulated in ESCC tumors. Using small interfering RNAs and CRISPR–Cas9 methods, we identified that both knockdown and knockout of TNXB significantly promoted ESCC cell growth in vitro, suggesting a tumor suppressor role of this gene in ESCC. Through further fine‐mapping analysis, we identified that a noncoding variant in the promoter of TNXB, rs411337, predisposed to ESCC risk (odds ratio = 1.36, 95% confidence interval: 1.22‐1.51, P = 9.10 × 10−9). These findings revealed the functional mechanism of TNXB in the development of ESCC and may contribute to the prevention and treatment of this disease in the future.

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“…DNA was isolated from the blood sample using a TIANamp Blood DNA Kit (TianGen Biotech Co. Ltd.). Then, the DNA was further performed to genotype using the TaqMan methodology instructed by the manufacturers . Negative controls (water samples) were used to ensure genotyping preciseness.…”

Section: Methodsmentioning

confidence: 99%

LIN28A gene polymorphisms modify neuroblastoma susceptibility: A four‐centre case‐control study

Hua

Zhang

et al. 2019

J Cellular Molecular Medi

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Neuroblastoma ranks the most common seen solid tumour in childhood. Overexpression of LIN28A gene has been linked to the development of multiple human malignancies, but the relationship between LIN28A single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility is still under debate. Herein, we evaluated the correlation of four potentially functional LIN28A SNPs (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) and neuroblastoma susceptibility in 505 neuroblastoma patients and 1070 controls from four independent hospitals in China. The correlation strengths were determined by using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Among these SNPs, rs34787247 G>A exhibited a significant association with increased susceptibility in neuroblastoma (GA vs GG: adjusted OR = 1.30, 95% CI = 1.03‐1.64; AA vs GG: adjusted OR = 2.51, 95% CI = 1.36‐4.64, AA/GA vs GG: adjusted OR = 1.42, 95% CI = 1.12‐1.80, AA vs GG/GA: adjusted OR = 2.39, 95% CI = 1.29‐4.42). Furthermore, the combined analysis of risk genotypes revealed that subjects carrying three risk genotypes (adjusted OR = 1.64, 95% CI = 1.02‐2.63) are more inclined to develop neuroblastoma than those without risk genotype, and so do carriers of 1‐4 risk genotypes (adjusted OR = 1.26, 95% CI = 1.01‐1.56). Stratification analysis further revealed risk effect of rs3811464 G>A, rs34787247 G>A and 1‐4 risk genotypes in some subgroups. Haplotype analysis of these four SNPs yields two haplotypes significantly correlated with increased neuroblastoma susceptibility. Overall, our finding indicated that LIN28A SNPs, especially rs34787247 G>A, may increase neuroblastoma risk.

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Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma

Cited by 80 publications

References 64 publications

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

A functional variant in TNXB promoter associates with the risk of esophageal squamous‐cell carcinoma

LIN28A gene polymorphisms modify neuroblastoma susceptibility: A four‐centre case‐control study

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