ALKBH5 Gene Polymorphisms and Hepatoblastoma Susceptibility in Chinese Children

Incidence of hepatoblastoma has been increasing, but the causes of this disease remain unclear. Some studies have suggested that abnormal expressions of ALKBH5 gene are associated with multiple cancers. This study aims to test the hypothesis that hepatoblastoma risk may be modulated by genetic polymorphisms in ALKBH5 gene based on genotyped data from samples of 328 cases and 1476 controls enrolled from eight hospitals in China. We used TaqMan assay to genotype ALKBH5 gene single nucleotide polymorphisms (SNPs) rs1378602G > A and rs8400G > A. We calculated the odds ratios (ORs) and P values using logistic regression models to estimate the association between hepatoblastoma risk and ALKBH5 gene SNPs. We found the rs1378602G > A and rs8400G > A could not impact hepatoblastoma risk in single or combined analysis. Stratified analysis revealed that subjects with the rs8400 AA genotype are prone to getting hepatoblastoma in the clinical stage III + IV subgroup (adjusted OR = 1.93, 95% CI = 1.20–3.10, P = 0.007 ), when compared to those with GG/GA genotype. False-positive report probability validated the reliability of the significant results. Preliminary functional annotations revealed that rs8400 A is correlated with increased expression of ALKBH5 gene in the expression quantitative trait locus (eQTL) analysis. In all, our investigation presents evidence of a weak impact of ALKBH5 gene polymorphisms on hepatoblastoma risk, using the largest hepatoblastoma sample size. These findings shed some light on the genetic basis of hepatoblastoma, implicating the role of ALKBH5 gene polymorphisms in the etiology of hepatoblastoma.

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Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer

Journal of Dental Research ◽

10.1177/0022034517749451 ◽

2018 ◽

Vol 97 (6) ◽

pp. 717-724 ◽

Cited By ~ 23

Author(s):

S.C. Su ◽

M.J. Hsieh ◽

C.W. Lin ◽

C.Y. Chuang ◽

Y.F. Liu ◽

...

Keyword(s):

Oral Cancer ◽

Odds Ratio ◽

Gene Polymorphisms ◽

Clinical Stage ◽

Interactive Effect ◽

Clinical Status ◽

Betel Quid ◽

Nucleotide Polymorphisms ◽

Advanced Clinical Stage ◽

Betel Quid Chewing

Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene— rs920778, rs1899663, rs4759314, and rs12427129—were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non–betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non–betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.

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Identification of a functional genetic variant driving racially dimorphic platelet gene expression of the thrombin receptor regulator, PCTP

Thrombosis and Haemostasis ◽

10.1160/th16-09-0692 ◽

2017 ◽

Vol 117 (05) ◽

pp. 962-970 ◽

Cited By ~ 4

Author(s):

Xianguo Kong ◽

Lukas Simon ◽

Michael Holinstat ◽

Chad Shaw ◽

Paul Bray ◽

...

Keyword(s):

Gene Expression ◽

Allelic Frequency ◽

Expression Level ◽

Eqtl Analysis ◽

Nucleotide Polymorphisms ◽

Genomic Locus ◽

Single Nucleotide ◽

Single Nucleotide Change ◽

Public Data ◽

Trait Locus

SummaryPlatelet activation in response to stimulation of the Protease Activated Receptor 4 (PAR4) receptor differs by race. One factor that contributes to this difference is the expression level of Phosphatidylcholine Transfer Protein (PCTP), a regulator of platelet PAR4 function. We have conducted an expression Quantitative Trait Locus (eQTL) analysis that identifies single nucleotide polymorphisms (SNPs) linked to the expression level of platelet genes. This analysis revealed 26 SNPs associated with the expression level of PCTP at genome-wide significance (p < 5×10–8). Using annotation from ENCODE and other public data we prioritised one of these SNPs, rs2912553, for functional testing. The allelic frequency of rs2912553 is racially-dimorphic, in concordance with the racially differential expression of PCTP. Reporter gene assays confirmed that the single nucleotide change caused by rs2912553 altered the transcriptional potency of the surrounding genomic locus. Electromobility shift assays, luciferase assays, and overexpression studies indicated a role for the megakaryocytic transcription factor GATA1. In summary, we have integrated multi-omic data to identify and functionalise an eQTL. This, along with the previously described relationship between PCTP and PAR4 function, allows us to characterise a genotype-phenotype relationship through the mechanism of gene expression.

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METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children

BMC Cancer ◽

10.1186/s12885-021-09019-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhenjian Zhuo ◽

Rui-Xi Hua ◽

Huizhu Zhang ◽

Huiran Lin ◽

Wen Fu ◽

...

Keyword(s):

Genetic Variants ◽

Gene Polymorphisms ◽

Haplotype Analysis ◽

Wilms Tumor ◽

Joint Analysis ◽

Protective Effects ◽

Genetic Modifiers ◽

Tumor Susceptibility ◽

Positive Report ◽

Stratified Analysis

Abstract Background Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility. Methods A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay. Result Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0–4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes. Conclusions Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

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Association Between LIN28A Gene Polymorphisms and Glioma Susceptibility in Chinese Children

Cancer Control ◽

10.1177/10732748211040009 ◽

2021 ◽

Vol 28 ◽

pp. 107327482110400

Author(s):

Huiqin Guo ◽

Yuxiang Liao ◽

Ao Lin ◽

Huiran Lin ◽

Xiaokai Huang ◽

...

Keyword(s):

Gene Polymorphisms ◽

Case Control Study ◽

Malignant Tumors ◽

Clinical Stage ◽

Case Control ◽

Chinese Children ◽

Stage Iii ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Control Study

Gliomas are the most prevalent brain tumors among children and adolescents. The occurrence and development of various malignant tumors is closely related with LIN28A gene, but its relationship with glioma susceptibility has not been widely discovered. In this case-control study, we conducted four single nucleotide polymorphisms (SNPs) (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) of LIN28A gene to investigate whether they increase the risk of glioma. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate their relationship. There was no significant correlation between four SNPs and glioma risk in single polymorphism and conjoint analysis. However, in stratification analysis, we found that rs3811463 TC/CC may add to the risk of glioma with clinical stage III (adjusted OR = 3.16, 95% CI = 1.15-8.70, P = .026) or stage III+IV patients (adjusted OR = 2.05, 95% CI = 1.02-4.13, P = .044). Our research suggested that four SNPs of LIN28A gene have a weak relationship with the risk of glioma in Chinese children. LIN28A rs3811463 TC/CC may increase the possibility of glioma in clinical stage III or stage III+IV patients which need larger samples and further confirmation.

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RIPK1 Polymorphisms Alter the Susceptibility to Cervical Cancer among the Uyghur population in China

10.21203/rs.2.15722/v2 ◽

2020 ◽

Author(s):

Lili Han ◽

Sulaiya Husaiyin ◽

Chunhua Ma ◽

Mayinuer Niyazi

Keyword(s):

Cervical Cancer ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Clinical Stage ◽

Binary Logistic Regression ◽

Interacting Protein ◽

Logistic Regression Models ◽

Cervical Cancer Risk ◽

Uyghur Population ◽

Stratified Analysis

Abstract Background: RIPK1 (receptor-interacting protein kinase-1) plays a role in cancer development, whereas no clear studies focused on the cervical cancer. The objective of this study was to evaluate the relationship between RIPK1 polymorphisms and cervical cancer risk among the Uyghur population. Methods: We performed a case-control study including 342 cervical cancer patients and 498 age-matched healthy controls. Four RIPK1 genetic variants (rs6907943, rs2077681, rs9503400 and rs17548629) were genotyped with Agena MassARRAY platform. The associations between RIPK1 polymorphisms and cervical cancer risk were assessed under Binary logistic regression models. False discovery rate (FDR) was used to improve the results reliability. Results: The results showed rs2077681 was significantly associated with cervical cancer risk under various genetic models (codominant: OR = 3.14, 95% CI = 1.40-7.07, p = 0.006, FDR- p = 0.018; recessive: OR = 3.20, 95% CI = 1.43-7.16, p = 0.005, FDR-0.018). The stratified analysis indicated that the relationships of rs6907946, rs9503400 and rs17548629 with cervical cancer risk were statistically significant in the subgroup of clinical stage ( p < 0.05). Conclusion: Our findings demonstrated that RIPK1 polymorphisms were associated with cervical cancer susceptibility among the Uyghur population in China, and RIPK1 polymorphisms might be involved in the development of cervical cancer.

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Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types

Nucleic Acids Research ◽

10.1093/nar/gkaa1190 ◽

2020 ◽

Author(s):

Junyi Xin ◽

Mulong Du ◽

Xia Jiang ◽

Yanling Wu ◽

Shuai Ben ◽

...

Keyword(s):

Genetic Variants ◽

Genome Wide Association Study ◽

The Cancer Genome Atlas ◽

Systematic Evaluation ◽

Eqtl Analysis ◽

Nucleotide Polymorphisms ◽

Cancer Etiology ◽

Functional Roles ◽

Cancer Types ◽

Trait Locus

Abstract PIWI-interacting RNAs (piRNAs) are an emerging class of non-coding RNAs involved in tumorigenesis. Expression quantitative trait locus (eQTL) analysis has been demonstrated to help reveal the genetic mechanism of single nucleotide polymorphisms (SNPs) in cancer etiology. However, there are no databases that have been constructed to provide an eQTL analysis between SNPs and piRNA expression. In this study, we collected genotyping and piRNA expression data for 10 997 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Using linear regression cis-eQTL analysis with adjustment of appropriate covariates, we identified millions of SNP-piRNA pairs in tumor (76 924 831) and normal (24 431 061) tissues. Further, we performed differential expression and survival analyses, and linked the eQTLs to genome-wide association study (GWAS) data to comprehensively decipher the functional roles of identified cis-piRNA eQTLs. Finally, we developed a user-friendly database, piRNA-eQTL (http://njmu-edu.cn:3838/piRNA-eQTL/), to help users query, browse and download corresponding eQTL results. In summary, piRNA-eQTL could serve as an important resource to assist the research community in understanding the roles of genetic variants and piRNAs in the development of cancers.

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Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-314483 ◽

2019 ◽

Vol 104 (10) ◽

pp. 1467-1471

Author(s):

Meng Lv ◽

Handan Tan ◽

Jing Deng ◽

Liping Du ◽

Guannan Su ◽

...

Keyword(s):

Gene Polymorphisms ◽

Han Chinese ◽

Nucleotide Polymorphisms ◽

Toll Like Receptor ◽

Single Nucleotide ◽

P Values ◽

Band Keratopathy ◽

Stratified Analysis ◽

Genotype And Allele Frequencies ◽

Paediatric Uveitis

AimsWe aimed to determine whether paediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis associated paediatric uveitis (JIA-PU) have an association with Toll-like receptor 10 (TLR10) gene polymorphisms in Han Chinese.MethodsTen tag single nucleotide polymorphisms (SNPs) of TLR10 were analysed in 992 PIU patients, 127 JIA-PU patients and 1600 controls using the Sequenom MassARRAY system and iPLEX Gold assay. Genotype and allele frequencies were analysed using the χ2 test. A stratified analysis was performed according to the clinical features of PIU.ResultsIncreased frequencies of the rs2101521 A allele, rs10004195 A allele, rs11725309 CC genotype and rs6841698 AA genotype were found in PIU patients compared with controls (corrected p values (Pc)=1.81×10-4, Pc= 1.12×10-2, Pc=2.41×10-2 and Pc=3.29×10-3, respectively). There was no association between these 10 tag SNPs and JIA-PU. In the stratified analysis, the frequency of the rs6841698 A allele was higher in PIU patients with cataract (Pc=1.45×10-6). The frequencies of the rs2101521 A allele and rs6841698 AA genotype were increased in PIU patients with band keratopathy (BK) (Pc=2.32×10-2, Pc=3.30×10-3, respectively).ConclusionTLR10 gene polymorphisms (rs2101521, rs10004195, rs11725309 and rs6841698) confer susceptibility to PIU in Han Chinese. In a stratified analysis, rs2101521 and rs6841698 are associated with PIU with BK, and rs6841698 correlates with PIU with cataract.

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H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study

10.21203/rs.2.23509/v1 ◽

2020 ◽

Author(s):

Wenya Li ◽

Rui-Xi Hua ◽

Mi Wang ◽

Da Zhang ◽

Jinhong Zhu ◽

...

Keyword(s):

Wilms Tumor ◽

Clinical Stage ◽

Genetic Variations ◽

Nucleotide Polymorphisms ◽

Predisposing Factor ◽

Single Nucleotide ◽

Tumor Risk ◽

H19 Gene ◽

Stratified Analysis ◽

Control Study

Abstract Background: Wilms tumor is the most common pediatric renal cancer. However, genetic bases behind Wilms tumor remain largely unknown. H19 is a critical maternally imprinted gene. Previous studies indicated that Single nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallele silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility.Methods: We conducted a four-center study to investigate whether H19 SNPs was a predisposing factor to Wilms tumor. Three polymorphisms in the H19 (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) were genotyped in 355 cases and 1070 cancer-free controls,using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.Results: We found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. Carriers of 1, 2 and 1-2 risk genotypes were inclined to develop Wilms tumor compared with those without risk genotype [adjusted odds ratio (OR)=1.36, 95% confidence interval (CI)=1.02-1.80, P =0.037; adjusted OR=1.84, 95% CI=1.27-2.67, P =0.001; adjusted OR=1.50, 95% CI=1.17-1.92, P =0.002, respectively]. The stratified analysis further revealed that rs2839698 AA, rs217727 AA, and 1-2 risk genotypes could strongly increase Wilms tumor risk among children above 18 months of age, males, and with clinical stage I+II disease.Conclusion: Our findings indicate that genetic variations in the H19 may confer Wilms tumor risk.

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YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study

Frontiers in Medicine ◽

10.3389/fmed.2021.797195 ◽

2021 ◽

Vol 8 ◽

Author(s):

Huijuan Zeng ◽

Meng Li ◽

Jiabin Liu ◽

Jinhong Zhu ◽

Jiwen Cheng ◽

...

Keyword(s):

Cancer Progression ◽

Case Control Study ◽

Clinical Stage ◽

Stage Iv ◽

Rna Modification ◽

Close Attention ◽

Primary Malignancy ◽

Trait Locus ◽

Positive Report ◽

Control Study

Neuroblastoma is a primary malignancy mainly occurring in children. We have reported that polymorphisms of several N6-methyladenosine (m6A) RNA modification-related genes contributed to neuroblastoma risk in previous studies. YTHDF2, a “reader” of RNA m6A modification, is involved in cancer progression. Here, we estimated the association between a YTHDF2 gene rs3738067 A>G polymorphism and neuroblastoma susceptibility in 898 neuroblastoma patients and 1,734 healthy individuals from China. We found that the rs3738067 A>G could decrease neuroblastoma risk [AG vs. AA: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.64–0.90, P = 0.002; AG/GG vs. AA: adjusted OR = 0.81, 95% CI = 0.69–0.95, P = 0.011). Besides, the rs3738067 AG/GG genotype was related to reduced neuroblastoma risk in the following subgroups: children aged 18 months and under, boys, patients with tumors originating from retroperitoneal, patients at clinical stage IV, and cases at clinical stages III plus IV. Importantly, false-positive report probability analysis proved our significant results worthy of close attention of. The expression quantitative trait locus analysis results revealed that the rs3738067 was associated with the expression of YTHDF2.

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Variants in RETN gene are associated with Steroid-induced osteonecrosis of the femoral head risk among Han Chinese People

10.21203/rs.2.15695/v1 ◽

2019 ◽

Author(s):

Feimeng An ◽

Litian Zhang ◽

Hongyan Gao ◽

Jiaqi Wang ◽

Chang Liu ◽

...

Keyword(s):

Lipid Metabolism ◽

Femoral Head ◽

Clinical Stage ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Stratified Analysis ◽

Significant Linkage ◽

Control Study

Abstract Introduction Gene polymorhisms has an important influence on RETN gene expression level, and the increased level of resistin encoded in RETN will lead to metabolic disorder, especially lipid metabolism. Moreover, steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is closely related to lipid metabolism level, so this study aims to explore the association of RETN Polymorphisms with susceptibility to steroid-induced ONFH in the Chinese Han Population.Methods In this case-control study, eight single nucleotide polymorphisms (SNPs) of RETN were genotyped by Agena MassARRAY system in 199 steroid-induced ONFH patients and 200 healthy controls. The association between RETN polymorphisms and steroid-induced ONFH risk was evaluated using genetic models and haplotype analyses. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age.Results We found significant differences in the distribution of HDL-C, TG/HDL-C, and LDL-C/HDL-C between the patients and the control group (p < 0.05). In allele model and genotype model analysis, rs34861192, rs3219175, rs3745368 and rs1477341 could reduce the risk of steroid-induced ONFH. Further stratified analysis showed that rs3745367 was related to the clinical stage of patients, and rs1477341 was significantly correlated with an increased TG level and a decreased TC/ HDL-C level. The Linkage analysis showed that three SNPs (rs34861192, rs3219175) in RETN even significant linkage disequilibrium.Conclusions Our results provide the firstly evidence that RETN gene polymorphisms were associated with a reduced risk of steroid-induced ONFH in Chinese Han Population.

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