Wu Tiantian, Shi Ziang, Fida Saba, Zhou Mingming, Zou Yuanlin, Zhang Shaobo, Cheng Haoqing, Guo Pengxia, Zhang Chuying, Zhang Gege, Song Chunhua
Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, China.
Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan, China.
Clin Breast Cancer. 2025 Apr;25(3):e260-e269.e19. doi: 10.1016/j.clbc.2024.11.008. Epub 2024 Nov 17.
Methyltransferase-like 3/14/16 (METTL3/14/16) presents the regulating valve in N6-methyladenosine (mA) modification, involved in carcinogenesis. We addressed elucidating the relationship between single-nucleotide polymorphisms (SNPs) of the METTL3/14/16 gene and breast cancer (BC) susceptibility.
A case-control study included 680 BC patients and 680 healthy controls, individually matched for age (±2 years).
7 SNPs were screened by bioinformatics tools. Conditional Logistic analysis was used to explore the association between SNPs and BC susceptibility. SNPs-reproductive factors interaction was assessed. qRT-PCR was conducted to detect the METTL3/14/16 expression of different SNPs. The potential biomechanism was explored using bioinformatics tools.
Among the 7 analyzed SNPs, METTL3 rs1061026 T>G exhibited a significant association with reduced susceptibility to BC. The TC+CC genotype of METTL14 rs428409 elevated BC risk, while the AG+GG genotype of METTL14 rs3087958 restrained BC risk. The stratified analysis further identified the protective effect of rs1061026 T>G and rs3087958 T>G, and the detrimental effect of rs428409 T>G in specific subgroups. Haplotype analysis revealed that haplotypes GC and GTrG were protective for BC. BC patients who carried the C allele in METTL14 rs428409 were more likely to be HER-2 positive. Individuals with age at menarche ≥14, number of pregnancies >1, and G allele in rs1061026 had a 47.7% decreased risk of BC. There were considerable multiplicative interactions between SNPs and reproductive factors. The relative expression of METTL3/14 was altered due to rs1061026 T>G, rs428409 T>C, and rs3087958 A>G. These three SNPs might interfere with the mA modification and the expression level of BC-related genes.
Our findings suggested that rs1061026 T>G, rs428409 T>C, and rs3087958 A>G might be associated with the risk of BC.
甲基转移酶样蛋白3/14/16（METTL3/14/16）是N6-甲基腺苷（m⁶A）修饰的调节阀，参与肿瘤发生。我们旨在阐明METTL3/14/16基因单核苷酸多态性（SNP）与乳腺癌（BC）易感性之间的关系。
一项病例对照研究纳入了680例BC患者和680名健康对照，年龄个体匹配（±2岁）。
通过生物信息学工具筛选出7个SNP。采用条件Logistic分析来探究SNP与BC易感性之间的关联。评估SNP与生殖因素的相互作用。进行qRT-PCR以检测不同SNP的METTL3/14/16表达。使用生物信息学工具探索潜在的生物机制。
在分析的7个SNP中，METTL3 rs1061026 T>G与BC易感性降低显著相关。METTL14 rs428409的TC+CC基因型增加了BC风险，而METTL14 rs3087958的AG+GG基因型降低了BC风险。分层分析进一步确定了rs1061026 T>G和rs3087958 T>G的保护作用，以及rs428409 T>G在特定亚组中的有害作用。单倍型分析显示单倍型GC和GTrG对BC具有保护作用。在METTL14 rs428409中携带C等位基因的BC患者更可能为HER-2阳性。初潮年龄≥14岁、怀孕次数>1次且rs1061026中携带G等位基因的个体患BC的风险降低47.7%。SNP与生殖因素之间存在显著的相乘相互作用。由于rs1061026 T>G、rs428409 T>C和rs3087958 A>G，METTL3/14的相对表达发生改变。这三个SNP可能会干扰m⁶A修饰以及BC相关基因的表达水平。
我们的研究结果表明，rs1061026 T>G、rs428409 T>C和rs3087958 A>G可能与BC风险相关。
