Tiantian Wu, Ziang Shi, Saba Fida, Mingming Zhou, Yuanlin Zou, Shaobo Zhang, Haoqing Cheng, Pengxia Guo, Chuying Zhang, Gege Zhang, Chunhua Song
{"title":"METTL3/14/16基因多态性对中国女性乳腺癌风险的影响","authors":"Tiantian Wu, Ziang Shi, Saba Fida, Mingming Zhou, Yuanlin Zou, Shaobo Zhang, Haoqing Cheng, Pengxia Guo, Chuying Zhang, Gege Zhang, Chunhua Song","doi":"10.1016/j.clbc.2024.11.008","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Methyltransferase-like 3/14/16 (METTL3/14/16) presents the regulating valve in N6-methyladenosine (m<sup>6</sup>A) 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.</p><p><strong>Study design: </strong>A case-control study included 680 BC patients and 680 healthy controls, individually matched for age (±2 years).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 G<sub>rs1061026</sub>C<sub>rs1061027</sub> and G<sub>rs368669</sub>Tr<sub>s428409</sub>G<sub>rs3087958</sub> 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 m<sup>6</sup>A modification and the expression level of BC-related genes.</p><p><strong>Conclusion: </strong>Our findings suggested that rs1061026 T>G, rs428409 T>C, and rs3087958 A>G might be associated with the risk of BC.</p>","PeriodicalId":10197,"journal":{"name":"Clinical breast cancer","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of METTL3/14/16 Gene Polymorphisms on Risk of Breast Cancer in Chinese Women.\",\"authors\":\"Tiantian Wu, Ziang Shi, Saba Fida, Mingming Zhou, Yuanlin Zou, Shaobo Zhang, Haoqing Cheng, Pengxia Guo, Chuying Zhang, Gege Zhang, Chunhua Song\",\"doi\":\"10.1016/j.clbc.2024.11.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Methyltransferase-like 3/14/16 (METTL3/14/16) presents the regulating valve in N6-methyladenosine (m<sup>6</sup>A) 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.</p><p><strong>Study design: </strong>A case-control study included 680 BC patients and 680 healthy controls, individually matched for age (±2 years).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 G<sub>rs1061026</sub>C<sub>rs1061027</sub> and G<sub>rs368669</sub>Tr<sub>s428409</sub>G<sub>rs3087958</sub> 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. 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引用次数: 0
摘要
目的：甲基转移酶样3/14/16 （METTL3/14/16）在n6 -甲基腺苷（m6A）修饰中发挥调控作用，参与肿瘤发生。我们致力于阐明METTL3/14/16基因的单核苷酸多态性（snp）与乳腺癌（BC）易感性之间的关系。研究设计：病例对照研究包括680名BC患者和680名健康对照者，年龄（±2岁）匹配。方法：采用生物信息学方法筛选7个snp。采用条件Logistic分析探讨snp与BC易感性之间的关系。评估snp与生殖因子的相互作用。采用qRT-PCR检测不同snp的METTL3/14/16表达情况。利用生物信息学工具探讨了潜在的生物机制。结果：在分析的7个snp中，METTL3 rs1061026 T b> G与BC易感性降低显著相关。TC+CC基因型的METTL14 rs428409增加了BC风险，而AG+GG基因型的METTL14 rs3087958抑制了BC风险。分层分析进一步确定了rs1061026 T b> G和rs3087958 T>G的保护作用，以及rs428409 T>G在特定亚群中的有害作用。单倍型分析显示，Grs1061026Crs1061027和Grs368669Trs428409Grs3087958对BC具有保护作用。携带METTL14 rs428409中C等位基因的BC患者更有可能是HER-2阳性。初潮年龄≥14岁、怀孕次数≥110次、rs1061026基因中G等位基因的个体患BC的风险降低47.7%。snp与生殖因子之间存在大量的倍增性相互作用。由于rs1061026 T>G、rs428409 T>C和rs3087958 A>G， METTL3/14的相对表达量发生了改变。这三个snp可能会干扰m6A修饰和bc相关基因的表达水平。结论：rs1061026 T b> G、rs428409 T>C和rs3087958 A>G可能与BC发病风险相关。
Impact of METTL3/14/16 Gene Polymorphisms on Risk of Breast Cancer in Chinese Women.
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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