Document Type
Article
Abstract
Background DNA damage response genes (DDRG), implicated in several cancers as both predisposing risk factors as well as biomarkers for aggressiveness, have not been fully explored in multiple myeloma (MM).
Methods Herein, we analyzed disease associations of pathogenic variations in nine putative candidate genes using 3 446 MM cases and 323 233 cancer-free controls.
Results Increased MM risk was found to be associated with inherited rare pathogenic mutations in TP53, ATM, CHEK2, KDM1A, and ARID1A, with an enrichment of these variants among individuals with early onset or family history of MM. Individuals with TP53 or ATM germline mutations are also likely to have worse overall survival.
Conclusions Our results suggest expansion of the phenotypic spectrum of some of these DDRG to include MM. The identification of these germline predisposition genes opens the avenue for targeted screening of higher risk individuals especially those with young-onset or a family history of plasma cell gammopathies.
Digital Object Identifier (DOI)
Publication Info
Published in Journal of Hematology & Oncology, Volume 19, 2026.
Rights
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
APA Citation
Conry, M., Ostrovnaya, I., Kemel, Y., Sinha, S., Baughn, L. B., Avery, B., Maclachlan, K., Groner, V., Banaszak, L., Norman, A., Boddicker, N. J., Clay-Gilmour, A., Kumar, S., Kim, E., Dandiker, S., Waghmare, M., Slager, S., Sborov, D. W., Garber, J., & Brown, E. E. (2026). Multiple myeloma risk linked to DNA damage response genes. Journal of Hematology & Oncology, 19. https://doi.org/10.1186/s13045-025-01776-1