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Background <p>Wilms tumor is a highly heterogeneous tumor, and patients with high-risk Wilms tumor still do not have a good prognosis. DNA instability caused by abnormal genes in the base excision repair (BER) pathway is closely related to cancer. However, the important role of BER pathway gene variants in Wilms tumor remains largely unknown.</p> Methods <p>We enrolled 621 patients with Wilms tumor and 1737 controls from eight hospitals. We calculated odds ratios and 95% confidence intervals to evaluate the association strength. Stratification analysis was performed to further evaluate the associations of significant polymorphisms with the risk of Wilms tumor in different subgroups. False-positive report probability analysis was adopted to evaluate the robustness of the positive results. The associations of polymorphisms with gene expression were analyzed via eQTLs from the GTEx database.</p> Results <p>We found that the <i>FEN1</i> rs174538 GG, <i>FEN1</i> rs4246215 GG, <i>APEX1</i> rs3136817 CC, and <i>XRCC1</i> rs25487 TT genotypes were associated with an increased risk of Wilms tumor, whereas the <i>FEN1</i> rs4246215 TG/GG genotype was associated with a decreased risk. Stratification analysis revealed that significant polymorphisms remained associated with the risk of Wilms tumor in some subgroups. False-positive report probability analysis also revealed that some positive results were more robust. The eQTL results revealed that all four polymorphisms were associated with alterations in the expression of host or nearby genes.</p> Conclusions <p><i>FEN1</i> rs174538 A&gt;G, <i>FEN1</i> rs4246215 T&gt;G, <i>APEX1</i> rs3136817 T&gt;C, and <i>XRCC1</i> rs25487 C&gt;T are associated with Wilms tumor susceptibility, which provides potential molecular markers for the early diagnosis of Wilms tumor.</p>

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Genetic Variants in BER Pathway Genes Confer Wilms Tumor Susceptibility: New Insights from an Eight-Center Case-Control Study in Chinese Children

  • 期刊论文

  • 发表日期：

    2025年12月16日

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  • Sheng Zhu,
  • Jiahui Lai,
  • Lei Lin,
  • Haixia Zhou,
  • Yizhen Wang,
  • Hongting Lu,
  • Shouhua Zhang,
  • Shaohua He,
  • Chunlei Zhou,
  • Xun Liu,
  • Jing He,
  • Rui-Xi Hua,
  • Yong Li

摘要

Background

Wilms tumor is a highly heterogeneous tumor, and patients with high-risk Wilms tumor still do not have a good prognosis. DNA instability caused by abnormal genes in the base excision repair (BER) pathway is closely related to cancer. However, the important role of BER pathway gene variants in Wilms tumor remains largely unknown.

Methods

We enrolled 621 patients with Wilms tumor and 1737 controls from eight hospitals. We calculated odds ratios and 95% confidence intervals to evaluate the association strength. Stratification analysis was performed to further evaluate the associations of significant polymorphisms with the risk of Wilms tumor in different subgroups. False-positive report probability analysis was adopted to evaluate the robustness of the positive results. The associations of polymorphisms with gene expression were analyzed via eQTLs from the GTEx database.

Results

We found that the FEN1 rs174538 GG, FEN1 rs4246215 GG, APEX1 rs3136817 CC, and XRCC1 rs25487 TT genotypes were associated with an increased risk of Wilms tumor, whereas the FEN1 rs4246215 TG/GG genotype was associated with a decreased risk. Stratification analysis revealed that significant polymorphisms remained associated with the risk of Wilms tumor in some subgroups. False-positive report probability analysis also revealed that some positive results were more robust. The eQTL results revealed that all four polymorphisms were associated with alterations in the expression of host or nearby genes.

Conclusions

FEN1 rs174538 A>G, FEN1 rs4246215 T>G, APEX1 rs3136817 T>C, and XRCC1 rs25487 C>T are associated with Wilms tumor susceptibility, which provides potential molecular markers for the early diagnosis of Wilms tumor.