外显子组测序将HELB鉴定为非黏液性、非高级别浆液性上皮性卵巢癌的一个新的易感基因。
Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.
作者信息
Dicks Ed M, Tyrer Jonthan P, Ezquina Suzana, Jones Michelle, Baierl John, Peng Pei-Chen, Diaz Michael, Goode Ellen, Winham Stacey J, Dörk Thilo, Gorp Toon Van, Fazio Anna De, Bowtell David D L, Garsed Dale W, Odunsi Kunle, Moysich Kirsten, Pavanello Marina, Fostira Florentia, Webb Penelope M, Soukupová Jana, Cohen Paul A, Sieh Weiva, Fortner Renée Turzanski, Ricker Charite, Karlan Beth, Campbell Ian, Brenton James D, Ramus Susan J, Gayther Simon A, Pharoah Paul D P
机构信息
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Biomedical Sciences, Cedars-Sinai Medical Centre, Los Angeles, CA, USA.
出版信息
Eur J Hum Genet. 2025 Mar;33(3):297-303. doi: 10.1038/s41431-025-01786-0. Epub 2025 Feb 12.
Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.
少数DNA修复基因中的罕见种系功能丧失变异与上皮性卵巢癌有关。本研究的目的是评估全基因组中罕见的编码功能丧失变异在上皮性卵巢癌中的作用。我们使用来自2573例非黏液性病例和13923例对照的数据，对各种组织学类型进行了逐个基因的负荷测试。12个基因在错误发现率小于0.1时具有相关性，其中7个是已知的卵巢癌易感基因BRCA1、BRCA2、BRIP1、RAD51C、RAD51D、MSH6和PALB2。另外5个基因是OR2T35、HELB、MYO1A和GABRP，它们与非高级别浆液性卵巢癌相关，而MIGA1与高级别浆液性卵巢癌相关。对HELB相关性的进一步支持来自于以下观察结果：HELB中的功能丧失变异与自然绝经年龄相关，孟德尔随机化分析显示，基因预测的自然绝经年龄与子宫内膜样卵巢癌相关，但与高级别浆液性卵巢癌无关。
Zotero 插件