Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women
- 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
2025-08-21
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.