Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population
Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally. While m6A regulators are implicated in cancer progression, the role of single nucleotide polymorphisms (SNPs) in m6A regulator genes in HCC susceptibility remains underexplored. Here, we evaluated 3...
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Springer
2025-04-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02305-9 |
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| author | Guohua Ji Cize Gao Yi Yang Yuli Ding Ruining Liu Shuang Wu Xuelong Zhang Xiao Liang Songbin Fu Xiaobo Cui |
| author_facet | Guohua Ji Cize Gao Yi Yang Yuli Ding Ruining Liu Shuang Wu Xuelong Zhang Xiao Liang Songbin Fu Xiaobo Cui |
| author_sort | Guohua Ji |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally. While m6A regulators are implicated in cancer progression, the role of single nucleotide polymorphisms (SNPs) in m6A regulator genes in HCC susceptibility remains underexplored. Here, we evaluated 31 candidate SNPs across eight dysregulated m6A regulator genes in a case–control study comprising 800 HCC patients and 800 healthy controls from Northeast China. Genotyping revealed three SNPs significantly associated with elevated HCC risk: rs2736158 C allele (PRRC2A; adjusted odds ratio [OR] = 1.295, 95% [CI] = 1.039–1.615, p = 0.021), rs9366785 A allele (PRRC2A; adjusted odds ratio [OR] = 1.312, 95% [CI] = 1.011–1.704, p = 0.041), and rs274054 C allele (IGF2BP3; adjusted odds ratio [OR] = 1.224, 95% [CI] = 1.040–1.440, p = 0.015). Comparison of genotype frequency of three SNPs under given genetic models further linked rs274054 CC (IGF2BP3), rs2736158 CC (PRRC2A), and rs9366785 AA + AG (PRRC2A) genotypes to higher HCC risk. Subgroup analyses identified associations between specific genotypes (e.g., rs9906944 TT/TC in IGF2BP1) and adverse clinicopathological features, including vascular invasion and liver cirrhosis. Haplotype analysis highlighted the CACA haplotype (PRRC2A: rs280801, rs2736171, rs2736158, rs2736157) as a high-susceptibility marker (adjusted odds ratio [OR] = 1.297, 95% [CI] = 1.041–1.616, p = 0.020). Our findings suggest that m6A regulator SNPs contribute to HCC susceptibility and progression, offering insights into genetic biomarkers for risk stratification in Northeast Chinese populations. |
| format | Article |
| id | doaj-art-2d35a8f6d16d4b7f91d73edba56461b3 |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-2d35a8f6d16d4b7f91d73edba56461b32025-08-20T02:17:50ZengSpringerDiscover Oncology2730-60112025-04-0116111710.1007/s12672-025-02305-9Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese populationGuohua Ji0Cize Gao1Yi Yang2Yuli Ding3Ruining Liu4Shuang Wu5Xuelong Zhang6Xiao Liang7Songbin Fu8Xiaobo Cui9Laboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityLaboratory of Medical Genetics, Harbin Medical UniversityAbstract Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally. While m6A regulators are implicated in cancer progression, the role of single nucleotide polymorphisms (SNPs) in m6A regulator genes in HCC susceptibility remains underexplored. Here, we evaluated 31 candidate SNPs across eight dysregulated m6A regulator genes in a case–control study comprising 800 HCC patients and 800 healthy controls from Northeast China. Genotyping revealed three SNPs significantly associated with elevated HCC risk: rs2736158 C allele (PRRC2A; adjusted odds ratio [OR] = 1.295, 95% [CI] = 1.039–1.615, p = 0.021), rs9366785 A allele (PRRC2A; adjusted odds ratio [OR] = 1.312, 95% [CI] = 1.011–1.704, p = 0.041), and rs274054 C allele (IGF2BP3; adjusted odds ratio [OR] = 1.224, 95% [CI] = 1.040–1.440, p = 0.015). Comparison of genotype frequency of three SNPs under given genetic models further linked rs274054 CC (IGF2BP3), rs2736158 CC (PRRC2A), and rs9366785 AA + AG (PRRC2A) genotypes to higher HCC risk. Subgroup analyses identified associations between specific genotypes (e.g., rs9906944 TT/TC in IGF2BP1) and adverse clinicopathological features, including vascular invasion and liver cirrhosis. Haplotype analysis highlighted the CACA haplotype (PRRC2A: rs280801, rs2736171, rs2736158, rs2736157) as a high-susceptibility marker (adjusted odds ratio [OR] = 1.297, 95% [CI] = 1.041–1.616, p = 0.020). Our findings suggest that m6A regulator SNPs contribute to HCC susceptibility and progression, offering insights into genetic biomarkers for risk stratification in Northeast Chinese populations.https://doi.org/10.1007/s12672-025-02305-9M6AHepatocellular carcinomaSingle nucleotide polymorphismIGF2BP1IGF2BP3PRRC2A |
| spellingShingle | Guohua Ji Cize Gao Yi Yang Yuli Ding Ruining Liu Shuang Wu Xuelong Zhang Xiao Liang Songbin Fu Xiaobo Cui Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population Discover Oncology M6A Hepatocellular carcinoma Single nucleotide polymorphism IGF2BP1 IGF2BP3 PRRC2A |
| title | Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population |
| title_full | Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population |
| title_fullStr | Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population |
| title_full_unstemmed | Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population |
| title_short | Genetic variants in m6A regulator genes confer susceptibility and progression of HCC in a Northern Chinese population |
| title_sort | genetic variants in m6a regulator genes confer susceptibility and progression of hcc in a northern chinese population |
| topic | M6A Hepatocellular carcinoma Single nucleotide polymorphism IGF2BP1 IGF2BP3 PRRC2A |
| url | https://doi.org/10.1007/s12672-025-02305-9 |
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