N6-甲基腺苷（m6A）是一个动态、可逆的修饰过程，涉及一系列重要的生物学和病理生理过程，包括癌症的进展。在此，我们旨在评估 m6A 修饰基因的遗传变异与乙型肝炎病毒相关肝细胞癌 (HBV-HCC) 存活的关系。我们进行了两阶段生存分析，以研究 36 个 m6A 修饰基因中的 4425 个单核苷酸多态性 (SNP) 与 HBV-HCC 患者总生存 (OS) 的关联。然后，识别出的 SNP 进一步用于功能注释。我们发现 METTL3 rs1263790 (A > G) 和 ADARB1 rs57884102 (C > T) 与 HBV-HCC OS 显着相关（风险比 [HR] = 0.68，95% 置信区间 [CI] = 0.52-0.89，p = 0.004；HR = 1.70，95% CI = 1.33-2.18，p < 0.001）。综合分析显示，携带两种变异的风险基因型较多的患者的 OS 逐渐较差。此外，表达数量性状位点（eQTL）分析表明，rs1263790 G等位基因降低了483个细胞培养的成纤维细胞样本中METTL3的mRNA表达水平。我们发现HCC组织中METTL3和ADARB1的mRNA表达水平高于正常组织，并且较高的METTL3和较低的ADARB1与较差的HCC OS相关。我们的结果表明，两种新的遗传变异（METTL3 rs1263790 和 ADARB1 rs57884102）可能是 HBV-HCC 的潜在预后标志物，但这些结果需要在未来进行更大的不同种族队列和功能实验来验证。© 2024 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

N6-methyladenosine (m6A) is a dynamic and reversible modification process involving in a series of important biological and pathophysiological processes, including the progression of cancers. Herein, we aimed to assess the relationships of genetic variants in m6A modification genes with the survival of hepatitis B virus -related hepatocellular carcinoma (HBV-HCC). We performed a two-stage survival analysis to investigate the associations of 4425 single nucleotide polymorphisms (SNPs) in 36 m6A modification genes with the overall survival (OS) of HBV-HCC patients. Then, the identified SNPs were further used to functionally annotate. We identified that METTL3 rs1263790 (A > G) and ADARB1 rs57884102 (C > T) were significantly associated with the HBV-HCC OS (hazard ratios [HR] = 0.68, 95% confidence interval [CI] = 0.52-0.89, p = 0.004; and HR = 1.70, 95% CI = 1.33-2.18, p < 0.001, respectively). Combined analysis revealed that patients carrying more risk genotypes of two variants had a progressively poorer OS. Moreover, the expression quantitative trait loci (eQTL) analysis indicated that rs1263790 G allele decreased mRNA expression levels of METTL3 in 483 cell-cultured fibroblasts samples. And we found the mRNA expression levels of METTL3 and ADARB1 in HCC tissues were higher than in normal tissues, and the higher METTL3 and the lower ADARB1 were associated with poorer HCC OS. Our results demonstrated that two novel genetic variants (METTL3 rs1263790 and ADARB1 rs57884102) may be potential prognostic markers for HBV-HCC, but these results need larger different ethnic cohorts and functional experiments to validate in the future.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.