全外显子组测序确定FANCM是西班牙裔/拉丁裔女性雌激素受体阴性乳腺癌的一个易感基因。

Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women.

作者信息

Nierenberg Jovia L, Adamson Aaron W, Hu Donglei, Huntsman Scott, Patrick Carmina, Li Min, Steele Linda, Tao Shu, Ding Yuan Chun, Tong Barry, Shieh Yiwey, Fejerman Laura, Gruber Stephen B, Haiman Christopher A, John Esther M, Kushi Lawrence H, Torres-Mejía Gabriela, Ricker Charité, Weitzel Jeffrey N, Ziv Elad, Neuhausen Susan L

机构信息

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

出版信息

Nat Commun. 2025 Aug 21;16(1):7816. doi: 10.1038/s41467-025-60564-0.

DOI:10.1038/s41467-025-60564-0

PMID:40841357

Abstract

Breast cancer (BC) is one of the most common cancers globally. Genetic testing facilitates screening and informs targeted risk-reduction and treatments. However, genes included in testing panels are from European-ancestry studies. We conducted a pooled case-control analysis in self-identified Hispanic/Latina women (4178 cases and 4344 controls), using whole exome sequencing and a targeted panel. We tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. Using logistic regression, we found a strong association of LoF variants in FANCM with ER-negative BC (p = 4.1 × 10), odds ratio [confidence interval]: 6.7 [2.9-15.6]). Among known susceptibility genes, BRCA1, BRCA2, and PALB2 strongly associated with BC. FANCM was previously proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested clinically. Our results demonstrate that FANCM should be added to BC gene panels.

摘要

乳腺癌（BC）是全球最常见的癌症之一。基因检测有助于筛查，并为针对性的风险降低和治疗提供信息。然而，检测面板中包含的基因来自欧洲血统的研究。我们对自我认定的西班牙裔/拉丁裔女性（4178例病例和4344例对照）进行了一项汇总病例对照分析，使用全外显子测序和一个靶向检测面板。我们测试了功能丧失（LoF）变异与总体、雌激素受体（ER）阳性和ER阴性乳腺癌风险之间的关联。使用逻辑回归，我们发现FANCM基因中的LoF变异与ER阴性乳腺癌有很强的关联（p = 4.1×10，优势比[置信区间]：6.7 [2.9 - 15.6]）。在已知的易感基因中，BRCA1、BRCA2和PALB2与乳腺癌密切相关。FANCM此前被提议作为ER阴性乳腺癌的一个可能的易感基因，但临床上并不常规检测。我们的结果表明，FANCM应添加到乳腺癌基因检测面板中。