The correlation between <i><scp>LIN</scp>28B</i> gene potentially functional variants and Wilms tumor susceptibility in Chinese children

Fu, Wen; Liu, Guo-chang; Zhang, Zhao; Zhu, Jinhong; Jia, Wei Hua; Zhu, Shi-En; Hu, Jinhua; Wang, Fenghua; He, Jing; Xia, Hongmei

doi:10.1002/jcla.22200

Cited by 19 publications

(19 citation statements)

References 45 publications

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“…The 145 cases in the study were individuals newly diagnosed with neuroblastoma from the Guangzhou Women and Children’s Medical Center 19, 20, 21, 22, 23, 35. All tumors were histopathologically confirmed.…”

Section: Methodsmentioning

confidence: 99%

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: Methodsmentioning

confidence: 99%

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

Zhu

Jia

et al. 2018

Molecular Therapy - Nucleic Acids

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“…Most of the genetic variants are single nucleotide polymorphisms (SNPs). LIN28B polymorphisms were associated with Wilms tumor [22] and neuroblastoma [23] susceptibility in Chinese children. However, the relationship of LIN28B polymorphisms with hepatoblastoma susceptibility has not been investigated.…”

Section: Introductionmentioning

confidence: 95%

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

et al. 2020

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Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.

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“…Our previous epidemiological study showed that the LIN28B polymorphisms may be able to modify Wilms tumour susceptibility in Chinese children . As LIN28A is quite similar to LIN28B in either structure or cellular function, it is biologically plausible that LIN28A polymorphisms may also predispose to Wilms tumour.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we evaluated the association between the LIN28A polymorphisms and Our previous epidemiological study showed that the LIN28B polymorphisms may be able to modify Wilms tumour susceptibility in Chinese children. 15 As LIN28A is quite similar to LIN28B in either structure or cellular function, it is biologically plausible that LIN28A polymorphisms may also predispose to Wilms tumour. Our results indicated that rs3811463 CC/TC genotype and rs34787247 A allele confer an increased risk of Wilms tumour.…”

Section: Discussionmentioning

confidence: 99%

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

Zhang

Liu

et al. 2019

J Cellular Molecular Medi

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Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non‐carriers, subjects with 1 risk genotype and 1‐3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1‐3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour.

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The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children

Abstract: In summary, these results indicated that the LIN28B gene rs314276 C>A polymorphism alone and three combined polymorphisms may be able to modify WT susceptibility in Southern Chinese children. Our findings call for further validation in large studies with different ethnicities involved.

Cited by 19 publications

References 45 publications

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

Association between NER Pathway Gene Polymorphisms and Wilms Tumor Risk

LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

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