<i>ALKBH5</i> gene polymorphisms and Wilms tumor risk in Chinese children: A five‐center case‐control study

Hua, Rui‐Xi; Liu, Jiabin; Fu, Wen; Zhu, Jinhong; Zhang, Jiao; Cheng, Jiwen; Li, Suhong; Zhou, Haixia; Xia, Huimin; He, Jing; Zhang, Zhuo

doi:10.1002/jcla.23251

Cited by 24 publications

(25 citation statements)

References 46 publications

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“…N6‐methyladenosine (m 6 A), the most abundant and prevalent modification of mRNAs, has been demonstrated to significantly associate with gene expression 18 . An increasing number of m 6 A‐related cancers have been verified in recent years, including leukemia, 19 glioblastoma, 20 Wilms tumor, 21 bladder cancer, 22 endometrial cancer 23 and colorectal cancer 24 . M 6 A‐associated enzymes play a synergistic or opposite role in cancer progression 25 .…”

Section: Introductionmentioning

confidence: 99%

YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven‐center case–control study

Chen

et al. 2020

The Journal of Gene Medicine

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Background: Hepatoblastoma is a commonly occurring embryonal tumors in children. N6-methyladenosine (m 6 A) plays a critical role in gene expression, thus contributing to the occurrence and progression of cancer. RNA splicing is regulated by the nuclear m 6 A reader YTHDC1, yet the roles of YTHDC1 polymorphisms in hepatoblastoma remain unclear. Methods: We conducted a seven-center case-control study to determine the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C and rs3813832 T>C) and hepatoblastoma susceptibility. We recruited 313 hepatoblastoma patients and 1446 healthy controls. Results: There was no significant association between all of these polymorphisms and hepatoblastoma susceptibility in single locus or combined analysis. Stratification analysis revealed that rs2293596 TC/CC genotype carriers had a higher risk of developing hepatoblastoma in the subgroup of clinical stages III + IV [adjusted odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.18-2.76, p = 0.007]. In addition, 3 risk genotype carriers are more likely to develop hepatoblastoma in the subgroup of clinical stages III + IV (adjusted OR = 1.80, 95% CI = 1.18-2.76, p = 0.007). Furthermore, false-positive probability analysis was used to notarize our findings. Haplotype analysis indicated that there was no significant association between inferred haplotypes of YTHDC1 gene based on observed genotypes and hepatoblastoma risk. Conclusions: In conclusion, our findings suggest that the rs2293596 T>C polymorphism may contribute to hepatoblastoma susceptibly and YTHDC1 gene polymorphisms may have a cumulative effect on hepatoblastoma risk.

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Section: Introductionmentioning

confidence: 99%

YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven‐center case–control study

Chen

et al. 2020

The Journal of Gene Medicine

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“…For further mechanistic insight, we analyzed m6A-modifying enzymes in Wilms' tumor. Ao Lin et al has recently demonstrated that polymorphisms of the m6A methylase METTL3 are related with Wilms tumor susceptibility in Chinese children [23], and Rui-Xi Hua et al's work suggests that SNPs in the m6A demethylase ALKBH5 may exert a weak in uence on susceptibility to Wilms' tumor [24]. These studies analyzed only the possible relation between the WT and m6A "writers" and "erasers", though effects on "readers" in Wilms' tumor remained undetermined prior to our analysis.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

Liu

et al. 2021

Preprint

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Background Wilms’ tumor, also called nephroblastoma, is the most common pediatric renal malignancy. The pathogenesis of Wilms’ tumor has been attributed to several genetic and epigenetic factors. However, the most pervasive internal mRNA modification that affects almost every process of RNA metabolism, RNA N6-Methyladenosine (m6A) methylation, has not been characterized in Wilms’ tumor. Methods Wilms’ tumor (WT) and adjacent non-cancerous (NC) tissue samples were obtained from 23 children with nephroblastoma, and the global m6A levels were measured by mass spectrometry. Analyses by m6A-mRNA epitranscriptomic microarray and mRNA microarray were performed, and m6A-related mRNAs were validated by quantitative real-time PCR for input and m6A-immunoprecipitated RNA samples from WT and NC tissues. Gene ontology analysis and KEGG pathway analysis were performed for differentially expressed genes, and expression of RNA methylation-related factors was measured by quantitative real-time PCR. Results The total m6A methylation levels in total RNA of WT samples and NC samples were (0.21 ± 0.01)% and (0.22 ± 0.01)%, respectively, with no statistically significant difference. Fifty-nine transcripts were differentially m6A-methylated between the WT and NC groups, which showed distinct m6A modification patterns. Gene ontology analysis indicated that m6A-modified genes were enriched in cancer-associated pathways, including the mTOR pathway, and conjoint analysis of the unique methylation and gene expression patterns in WT samples suggested an association with metabolic pathways.The mRNA levels of the m6A-related “reader” genes, YTHDF1, YTHDF2 and IGF2BP3, were statistically higher in WT samples than in NC samples. Conclusion This is the first study to determine the m6A modification profiles in Wilms’ tumor. Our data provide novel information regarding patterns of m6A modification that correlate with carcinogenesis in Wilms’ tumor.

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“…In total, 414 patients and 1199 controls were enrolled from five regions in China, 31–33 for which the demographic characteristics and selection criteria have been described in detail in previous studies 34,35 . Briefly, patients were diagnosed with Wilms tumor based on the results of imaging and histopathological examinations, and the controls were healthy children whose age and sex were effectively matched to the patients (see Supporting information, Table S1).…”

Section: Methodsmentioning

confidence: 99%

METTL3 polymorphisms and Wilms tumor susceptibility in Chinese children: A five‐center case–control study

Zhou

Hua

et al. 2020

The Journal of Gene Medicine

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Background: Wilms tumor is a common pediatric tumor worldwide. Methyltransferase like 3 (METTL3) is a core gene of the N 6-methyladenosine (m 6 A) modification that widely affects the transcription of tumor-related genes in eukaryotes. METTL3 has been extensively investigated in various tumors but not Wilms tumor. Methods: We describe a five-center case-control study with 414 patients and 1199 controls aiming to explore the associations between METTL3 polymorphisms (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G and rs1263801 G>C) and Wilms tumor susceptibility. A TaqMan real-time polymerase chain reaction was performed for genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported as evaluation indicators to determine any associations. Results: Referring to the preliminary analysis results, protective genotypes were identified as rs1061026 TG/GG, rs1061027 CA/AA, rs1139130 GG and rs1263801 GC/CC. The children with three protective genotypes were less likely to develop Wilms tumor than children without protective genotypes (adjusted OR = 0.68, 95% CI = 0.46-0.999, p = 0.0496). Similarly, stratified analysis of the subgroup aged > 18 months, carrying 3 or 4 protective genotypes, was a protective factor for Wilms tumor compared to carrying 0-2 protective genotypes (adjusted OR = 0.59 95% CI = 0.39-0.91, p = 0.016). However, we did not observe any other significant results. Conclusions: The combined effect of METTL3 polymorphisms reduce Wilms tumor susceptibility in Chinese children. This conclusion requires further verification.

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ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five‐center case‐control study

Cited by 24 publications

References 46 publications

YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven‐center case–control study

YTHDC1 gene polymorphisms and hepatoblastoma susceptibility in Chinese children: A seven‐center case–control study

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

METTL3 polymorphisms and Wilms tumor susceptibility in Chinese children: A five‐center case–control study

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