靶向测序和功能询问鉴定了中国汉族女性卵巢癌风险相关的12q14.2新变异。

IF 2.9 3区 医学 Q2 ONCOLOGY
Yanrui Zhao, Wei Geng, Wei Liu, Lei Liu, Changcai Teng, Yuxin Chen, Dong Yang, Linqing Chai, Wei Wang, Xinlei Chu, Caiyun Huang, Ben Liu, Kexin Chen, Hong Zheng, Lian Li
{"title":"靶向测序和功能询问鉴定了中国汉族女性卵巢癌风险相关的12q14.2新变异。","authors":"Yanrui Zhao, Wei Geng, Wei Liu, Lei Liu, Changcai Teng, Yuxin Chen, Dong Yang, Linqing Chai, Wei Wang, Xinlei Chu, Caiyun Huang, Ben Liu, Kexin Chen, Hong Zheng, Lian Li","doi":"10.1093/carcin/bgaf037","DOIUrl":null,"url":null,"abstract":"<p><p>Chromosome 12q14.2 has been reported as a potential risk locus for epithelial ovarian cancer (EOC) in genome-wide association study (GWAS). We performed targeted sequencing around the rs11175194 at chromosome 12q14.2 and identified five potential risk variants. The association between these five variants and EOC risk was evaluated in 893 EOC cases and 1292 controls. We identified that rs11175195 (P = 1.94 × 10-6, OR = 1.36, 95% CI = 1.20-1.54) was significantly associated with EOC risk in validation study and after meta-analysis with previous GWAS data, rs11175195 reached genome-wide significant level (P < 5 × 10-8). Functional annotation and expression quantitative trait loci analysis prioritized rs11175194 as a causal variant at this locus. The presence of G-rs11175194 risk allele increased binding affinity of the transcription factor NR1H4 and upregulate SRGAP1 gene expression. Overexpression of SRGAP1 promotes the proliferation and invasion in ovarian cancer cell lines. In conclusion, we identified a novel susceptibility locus of ovarian cancer and revealed a potential molecular mechanism for ovarian cancer carcinogenesis. These results may provide a potential biomarker and therapeutic target for ovarian cancer.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeted sequencing and functional interrogation identified novel variant at 12q14.2 associated with risk of ovarian cancer in Han Chinese women.\",\"authors\":\"Yanrui Zhao, Wei Geng, Wei Liu, Lei Liu, Changcai Teng, Yuxin Chen, Dong Yang, Linqing Chai, Wei Wang, Xinlei Chu, Caiyun Huang, Ben Liu, Kexin Chen, Hong Zheng, Lian Li\",\"doi\":\"10.1093/carcin/bgaf037\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chromosome 12q14.2 has been reported as a potential risk locus for epithelial ovarian cancer (EOC) in genome-wide association study (GWAS). We performed targeted sequencing around the rs11175194 at chromosome 12q14.2 and identified five potential risk variants. The association between these five variants and EOC risk was evaluated in 893 EOC cases and 1292 controls. We identified that rs11175195 (P = 1.94 × 10-6, OR = 1.36, 95% CI = 1.20-1.54) was significantly associated with EOC risk in validation study and after meta-analysis with previous GWAS data, rs11175195 reached genome-wide significant level (P < 5 × 10-8). Functional annotation and expression quantitative trait loci analysis prioritized rs11175194 as a causal variant at this locus. The presence of G-rs11175194 risk allele increased binding affinity of the transcription factor NR1H4 and upregulate SRGAP1 gene expression. Overexpression of SRGAP1 promotes the proliferation and invasion in ovarian cancer cell lines. In conclusion, we identified a novel susceptibility locus of ovarian cancer and revealed a potential molecular mechanism for ovarian cancer carcinogenesis. These results may provide a potential biomarker and therapeutic target for ovarian cancer.</p>\",\"PeriodicalId\":9446,\"journal\":{\"name\":\"Carcinogenesis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Carcinogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/carcin/bgaf037\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/carcin/bgaf037","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

染色体12q14.2在全基因组关联研究(GWAS)中被报道为上皮性卵巢癌(EOC)的潜在危险位点。我们对12q14.2染色体上的rs11175194周围进行了靶向测序,确定了5个潜在的风险变异。在893例EOC病例和1292例对照中评估了这五种变异与EOC风险之间的关系。在验证研究中,我们发现rs11175195 (P = 1.94 × 10-6, OR = 1.36, 95% CI = 1.20 - 1.54)与EOC风险显著相关,在与之前的GWAS数据进行meta分析后,rs11175195达到全基因组显著水平(P < 5 × 10-8)。功能注释和表达数量性状位点(eQTL)分析优先考虑rs11175194作为该位点的因果变异。G-rs11175194风险等位基因的存在增加了转录因子NR1H4的结合亲和力,上调了SRGAP1基因的表达。SRGAP1过表达促进卵巢癌细胞系的增殖和侵袭。总之,我们发现了一个新的卵巢癌易感位点,并揭示了卵巢癌致癌的潜在分子机制。这些结果可能为卵巢癌提供潜在的生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeted sequencing and functional interrogation identified novel variant at 12q14.2 associated with risk of ovarian cancer in Han Chinese women.

Chromosome 12q14.2 has been reported as a potential risk locus for epithelial ovarian cancer (EOC) in genome-wide association study (GWAS). We performed targeted sequencing around the rs11175194 at chromosome 12q14.2 and identified five potential risk variants. The association between these five variants and EOC risk was evaluated in 893 EOC cases and 1292 controls. We identified that rs11175195 (P = 1.94 × 10-6, OR = 1.36, 95% CI = 1.20-1.54) was significantly associated with EOC risk in validation study and after meta-analysis with previous GWAS data, rs11175195 reached genome-wide significant level (P < 5 × 10-8). Functional annotation and expression quantitative trait loci analysis prioritized rs11175194 as a causal variant at this locus. The presence of G-rs11175194 risk allele increased binding affinity of the transcription factor NR1H4 and upregulate SRGAP1 gene expression. Overexpression of SRGAP1 promotes the proliferation and invasion in ovarian cancer cell lines. In conclusion, we identified a novel susceptibility locus of ovarian cancer and revealed a potential molecular mechanism for ovarian cancer carcinogenesis. These results may provide a potential biomarker and therapeutic target for ovarian cancer.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信