Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women
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-identifi...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60564-0 |
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| author | Jovia L. Nierenberg Aaron W. Adamson Donglei Hu Scott Huntsman Carmina Patrick Min Li Linda Steele Shu Tao Yuan Chun Ding Barry Tong Yiwey Shieh Laura Fejerman Stephen B. Gruber Christopher A. Haiman Esther M. John Lawrence H. Kushi Gabriela Torres-Mejía Charité Ricker Jeffrey N. Weitzel Elad Ziv Susan L. Neuhausen |
| author_facet | Jovia L. Nierenberg Aaron W. Adamson Donglei Hu Scott Huntsman Carmina Patrick Min Li Linda Steele Shu Tao Yuan Chun Ding Barry Tong Yiwey Shieh Laura Fejerman Stephen B. Gruber Christopher A. Haiman Esther M. John Lawrence H. Kushi Gabriela Torres-Mejía Charité Ricker Jeffrey N. Weitzel Elad Ziv Susan L. Neuhausen |
| author_sort | Jovia L. Nierenberg |
| collection | DOAJ |
| description | 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− 7), 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. |
| format | Article |
| id | doaj-art-0d05aa45e8a94fe5a97f207f9fec6a91 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0d05aa45e8a94fe5a97f207f9fec6a912025-08-24T11:36:43ZengNature PortfolioNature Communications2041-17232025-08-011611910.1038/s41467-025-60564-0Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina womenJovia L. Nierenberg0Aaron W. Adamson1Donglei Hu2Scott Huntsman3Carmina Patrick4Min Li5Linda Steele6Shu Tao7Yuan Chun Ding8Barry Tong9Yiwey Shieh10Laura Fejerman11Stephen B. Gruber12Christopher A. Haiman13Esther M. John14Lawrence H. Kushi15Gabriela Torres-Mejía16Charité Ricker17Jeffrey N. Weitzel18Elad Ziv19Susan L. Neuhausen20Department of Epidemiology and Biostatistics, University of California, San FranciscoDepartment of Population Sciences, Beckman Research Institute of City of HopeDepartment of Medicine, University of California, San FranciscoDepartment of Medicine, University of California, San FranciscoDepartment of Population Sciences, Beckman Research Institute of City of HopeDepartment of Medicine, University of California, San FranciscoDepartment of Population Sciences, Beckman Research Institute of City of HopeIntegrative Genomics Shared Resource, Beckman Research Institute of City of HopeDepartment of Population Sciences, Beckman Research Institute of City of HopeDepartment of Medicine, University of California, San FranciscoDepartment of Population Health Sciences, Weill Cornell MedicineDepartment of Public Health Service, University of California, DavisDepartment of Medical Oncology and Center for Precision Medicine, City of Hope National Medical CenterDepartment of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern CaliforniaDepartment of Epidemiology & Population Health, Stanford University School of MedicineDivision of Research, Kaiser Permanente Northern CaliforniaInstituto Nacional de Salud PúblicaDepartment of Medicine, Keck School of Medicine, University of Southern CaliforniaDivision of Precision Prevention, The University of Kansas Comprehensive Cancer CenterDepartment of Medicine, University of California, San FranciscoDepartment of Population Sciences, Beckman Research Institute of City of HopeAbstract 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− 7), 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.https://doi.org/10.1038/s41467-025-60564-0 |
| spellingShingle | Jovia L. Nierenberg Aaron W. Adamson Donglei Hu Scott Huntsman Carmina Patrick Min Li Linda Steele Shu Tao Yuan Chun Ding Barry Tong Yiwey Shieh Laura Fejerman Stephen B. Gruber Christopher A. Haiman Esther M. John Lawrence H. Kushi Gabriela Torres-Mejía Charité Ricker Jeffrey N. Weitzel Elad Ziv Susan L. Neuhausen Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women Nature Communications |
| title | Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women |
| title_full | Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women |
| title_fullStr | Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women |
| title_full_unstemmed | Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women |
| title_short | Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women |
| title_sort | whole exome sequencing identifies fancm as a susceptibility gene for estrogen receptor negative breast cancer in hispanic latina women |
| url | https://doi.org/10.1038/s41467-025-60564-0 |
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