YTHDF1 gene polymorphisms and neuroblastoma susceptibility in Chinese children: an eight-center case-control study

Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. is the critical downstream gene by which RNA m6A modification...

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Published inJournal of Cancer Vol. 12; no. 8; pp. 2465 - 2471
Main Authors Liu, Jiabin, Cheng, Jiwen, Li, Li, Li, Yong, Zhou, Haixia, Zhang, Jiao, Li, Suhong, Xia, Huimin, He, Jing, Yang, Zhonghua
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Published Australia Ivyspring International Publisher Pty Ltd 01.01.2021
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Abstract Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). In summary, our study indicates that gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
AbstractList Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. YTHDF1 is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the YTHDF1 gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the YTHDF1 gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, P =0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, P =0.018). In summary, our study indicates that YTHDF1 gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). In summary, our study indicates that gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. YTHDF1 is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the YTHDF1 gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the YTHDF1 gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). In summary, our study indicates that YTHDF1 gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. YTHDF1 is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the YTHDF1 gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the YTHDF1 gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). In summary, our study indicates that YTHDF1 gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. YTHDF1 is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the YTHDF1 gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the YTHDF1 gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). In summary, our study indicates that YTHDF1 gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
Author Li, Li
Liu, Jiabin
Zhou, Haixia
Zhang, Jiao
Cheng, Jiwen
Li, Yong
He, Jing
Li, Suhong
Yang, Zhonghua
Xia, Huimin
AuthorAffiliation 3 Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children's Hospital, Kunming 650228, Yunnan, China
1 Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
8 Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China
4 Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China
7 Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shannxi, China
2 Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China
5 Department of Hematology, T
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– name: 3 Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children's Hospital, Kunming 650228, Yunnan, China
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Keywords YTHDF1
m6A modification
polymorphism
neuroblastoma susceptibility
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Snippet Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure....
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StartPage 2465
SubjectTerms Age
Bladder cancer
Cancer therapies
DNA methylation
Gene expression
Genotype & phenotype
Medical prognosis
Metastasis
Neuroblastoma
Pediatrics
Regression analysis
Research Paper
Risk factors
Transcription factors
Tumorigenesis
Tumors
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Title YTHDF1 gene polymorphisms and neuroblastoma susceptibility in Chinese children: an eight-center case-control study
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