Correlation between the genetic variants of base excision repair (BER) pathway genes and neuroblastoma susceptibility in eastern Chinese children

Zhang, Zhuo; Zhou, Chunlei; Fang, Yuan; Zhu, Jinhong; Lu, Hongting; Zhou, Haixia; Wu, Haiyan; Wang, Yizhen; He, Jing

doi:10.1002/cac2.12088

Cited by 36 publications

(36 citation statements)

References 15 publications

(23 reference statements)

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“…Details on participants may be found in previous studies. 16 , 30 There were no significant differences between neuroblastoma patients and healthy controls in age (p = 0.823) and sex (p = 0.610).…”

Section: Resultsmentioning

confidence: 84%

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Association between NER pathway gene polymorphisms and neuroblastoma risk in an eastern Chinese population

Zhou

Wang

et al. 2021

Molecular Therapy - Oncolytics

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Neuroblastoma is a common childhood malignancy. Nucleotide excision repair (NER) polymorphisms have been shown to influence cancer susceptibility by modifying DNA repair efficiency. To investigate the association of NER gene polymorphisms with neuroblastoma risk, we constructed a three-center case-control study. A total of 19 candidate single-nucleotide polymorphisms (SNPs) in NER genes were analyzed. Odds ratios (ORs) and 95% confidential intervals (CIs) were calculated to evaluate the associations. We identified five independent SNPs that were significantly associated with neuroblastoma risk, including XPA rs1800975 (dominant model: adjusted OR = 0.73, 95% CI = 0.55–0.98, p = 0.033), XPA rs3176752 (recessive model: adjusted OR = 2.78, 95% CI = 1.12–6.91, p = 0.028), XPD rs3810366 (dominant: adjusted OR = 1.44, 95% CI = 1.05–1.97, p = 0.022; recessive: adjusted OR = 1.58, 95% CI = 1.18–2.11, p = 0.002), XPD rs238406 (dominant: adjusted OR = 0.64, 95% CI = 0.48–0.84, p = 0.002; recessive: adjusted OR = 0.67, 95% CI = 0.48–0.94, p = 0.021), and XPG rs2094258 (recessive: adjusted OR = 1.44, 95% CI = 1.03–2.04, p = 0.036). Stratified analysis was carried out. Furthermore, these findings were strengthened by false-positive report probability (FPRP) analysis and expression quantitative trait loci (eQTL) analysis. In conclusion, our study indicates that five SNPs in NER genes are correlated with neuroblastoma susceptibility in the eastern Chinese population, providing novel insight into the genetic underpinnings of neuroblastoma. However, further large-scale studies are required to verify these findings.

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Section: Resultsmentioning

confidence: 84%

“…A total of 313 neuroblastoma patients and 762 healthy controls from the eastern Chinese population were included in the case-control study. 16 , 30 , 44 All participants were unrelated Chinese Han children. The study was approved by each participating hospital Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

Association between NER pathway gene polymorphisms and neuroblastoma risk in an eastern Chinese population

Zhou

Wang

et al. 2021

Molecular Therapy - Oncolytics

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“…The present and previous results (21) indicate that C282Y HFE impacts neuroblastoma characteristics such as therapy resistance and cell proliferation. Several studies reported that single nucleotide polymorphisms (SNPs) in genes [e.g., ATP binding cassette subfamily C member 1 (ABCC1); caspase 8 (CASP8); ERCC excision repair 1, endonuclease non-catalytic subunit/ERCC excision repair 4, endonuclease non-catalytic subunit (ERCC1/XPF or ERCC1/ERCC4); poly(ADP-ribose) polymerase 1 (PARP1); base excision repair (BER); methyltransferase like 14 (METTL14)] are risk factors for neuroblastoma development and patient survival (40)(41)(42)(43)(44)(45). Our data indicate that the frequency of the C282Y HFE SNP in neuroblastoma patients should also be determined in future clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

et al. 2021

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Background/Aim: We have previously reported the identification of the cytotoxic chemotype compound-I (CC-I) from a chemical library screening against glioblastoma. Materials and Methods: The biological activity of CC-I on drug-resistant neuroblastomas [e.g., HFE gene variant C282Y stably transfected human neuroblastoma SH-SY5Y cells (C282Y HFE/SH-SY5Y), SK-N-AS] was characterized using cell culture models and in vivo mouse tumor models. Results: CC-I had potent cytotoxicity on therapy-resistant neuroblastoma cells and limited cytotoxicity on human primary dermal fibroblast cells. In addition, CC-I showed a robust anti-tumor effect on therapyresistant human neuroblastoma C282Y HFE/SH-SY5Y cells but not on SK-N-AS cells in a subcutaneous tumor model. CC-I induced phosphorylation of heat shock protein 27 (HSP27), protein kinase B (Akt), and c-Jun N-terminal kinase (JNK) in C282Y HFE/SH-SY5Y neuroblastoma cells. Conclusion: CC-I may be an effective therapeutic option for therapy-resistant neuroblastomas, especially if they express the C282Y HFE gene variant. Its anti-tumor effects are possibly through HSP27-Akt-JNK activation. Neuroblastoma is the second most common solid tumor discovered in children (1). It begins in the nerve cells outside of the brain, most often in the adrenal glands located on top of both kidneys. Nearly 90% of neuroblastomas are diagnosed by age 10 (2). In the United States, neuroblastoma occurs in about 800 children (age up to 14) each year, which accounts for 6% of all childhood cancers (3). The International Neuroblastoma Risk Group Staging System was developed by the International Neuroblastoma Risk Group for the standardization of neuroblastoma risk classification and for clinical trials (4). Risk factors for neuroblastoma include age at diagnosis, disease stage, tumor histology, and N-myc proto-oncogene protein (MYCN) amplification status (5). Although the 5-year survival rate for low-risk neuroblastoma is 95%, the 5-year survival rate for high-risk neuroblastoma is only 40-50% (3). About half of the neuroblastomas are metastatic at diagnosis, and advanced disease remains difficult to treat successfully despite the aggressive multimodality therapy. Treatment for neuroblastoma usually involves a variety of approaches such as chemotherapy, radiation, surgery, stem cell transplantation, biological agents, and immunotherapy (6, 7). The majority of patients with high-risk neuroblastoma will relapse despite receiving aggressive multimodal therapy, while an additional 10% to 20% will be refractory to induction therapy (8, 9). Because of disease heterogeneity among highrisk cases, subsequent management with salvage chemotherapy can be very challenging. Therefore, developing new treatment agents against neuroblastoma, especially therapy-resistant neuroblastoma, is urgently needed. We previously reported the identification of compound CC-I, a thiobarbituric acid derivative, from the screening of the ChemBridge small molecule library compounds, as an effective agent against drug-resistant glioblasto...

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“…Detailed information about SNPs selection and genotyping have been described previously. 41 , 42 , 43 …”

Section: Methodsmentioning

confidence: 99%

Genetic variants in m6A modification core genes are associated with glioma risk in Chinese children

Lin

et al. 2021

Molecular Therapy - Oncolytics

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Glioma is a highly heritable disease with a strong genetic component. The N6-methyladenosine (m 6 A) modification core genes play important roles in the context of cancer. However, the effects of polymorphisms in the m 6 A modification core genes on the risk of pediatric glioma remain undefined. Here, we intended to demonstrate the relationship between 24 functional single-nucleotide polymorphisms (SNPs) in eight m 6 A modification core genes and glioma risk. Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma while accounting for the subtypes of glioma. A total of 171 glioma cases and 228 controls from South China were genotyped using a TaqMan assay. The WTAP rs7766006, YTHDF2 rs3738067, and FTO rs9939609 variants conferred a statistically significant increased risk of glioma, respectively. YTHDC1 rs2293595, YTHDC1 rs3813832, and FTO rs8047395 were associated with a significant inverse association with risk of glioma, respectively. The significant associations were more predominant in stratification analyses of certain subgroups. Functional annotations revealed that WTAP rs7766006 and YTHDF 2 rs3738067 could be potential functional variants by increasing expression of WTAP and YTHDF2 mRNA, respectively. Overall, these findings implicate variants in the m 6 A modification core genes as playing a role in pediatric glioma etiology.

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Correlation between the genetic variants of base excision repair (BER) pathway genes and neuroblastoma susceptibility in eastern Chinese children

Cited by 36 publications

References 15 publications

Association between NER pathway gene polymorphisms and neuroblastoma risk in an eastern Chinese population

Association between NER pathway gene polymorphisms and neuroblastoma risk in an eastern Chinese population

Biological Activity of a Thiobarbituric Acid Compound in Neuroblastomas

Genetic variants in m6A modification core genes are associated with glioma risk in Chinese children

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