Tiantian Wu, Ziang Shi, Saba Fida, Mingming Zhou, Yuanlin Zou, Shaobo Zhang, Haoqing Cheng, Pengxia Guo, Chuying Zhang, Gege Zhang, Chunhua Song
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引用次数: 0
Abstract
Objectives: Methyltransferase-like 3/14/16 (METTL3/14/16) presents the regulating valve in N6-methyladenosine (m6A) 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.
Study design: A case-control study included 680 BC patients and 680 healthy controls, individually matched for age (±2 years).
Methods: 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.
Results: 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 Grs1061026Crs1061027 and Grs368669Trs428409Grs3087958 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 m6A modification and the expression level of BC-related genes.
Conclusion: Our findings suggested that rs1061026 T>G, rs428409 T>C, and rs3087958 A>G might be associated with the risk of BC.
期刊介绍：
Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.
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