biostudies-literatureNierenberg JLU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)7816https://www.ebi.ac.uk/biostudies/studies/S-EPMC12370925biostudies-literatureUnknown16(1)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 Nature communicationsWhole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women.PMC12370925K24CA169004R01CA184585R01CA120120Huntsman SPatrick CShieh YSteele LZiv EKushi LHLi MWeitzel JNTong BFejerman LGruber SBNierenberg JLHu DAdamson AWTao STorres-Mejia GNeuhausen SLHaiman CADing YCJohn EMRicker CfalseWhole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women.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 2025-01-01T00:00:00Z2025 Aug2026-05-08T10:41:52.543Z2026-04-07T23:46:37.766ZS-EPMC123709254084135710.1038/s41467-025-60564-0