Genetics amplify diabetes risk from alkylating agents in survivors

The research also suggested that another contributor to increased type 2 diabetes risk is exposure to alkylating agents, a class of chemotherapy commonly used in childhood cancer treatments. 

“We saw very consistently, in three out of our four identified variants, and all of our polygenic risk scores, a significant increase in diabetes risk when survivors were exposed to alkylating agents during their initial treatment,” Sapkota said. “So genetic factors in the presence of alkylating agents can significantly enhance type 2 diabetes risk.”

The alkylating agent effect also had a greater impact on those of African ancestry. While the reasons for these differences in risk remain unclear, the study is a step in the right direction toward addressing them.

“We hope this information will help reduce disparities in the type 2 diabetes burden,” Sapkota said. “Now we know how to identify childhood cancer survivors most at risk of type 2 diabetes so we can provide more personalized opportunities for interventions and prevent cardiovascular complications down the road.”

Authors and funding

The study’s first author is Cindy Im, University of Minnesota. The study’s other co-senior author is Carmen Wilson, St. Jude. The study’s other authors are Eric Chow, Fred Hutchinson Research Center; Sogol Mostoufi-Moab, Children’s Hospital of Philadelphia; Tianzhong Yang, University of Minnesota; Melissa Richard, M. Monica Gramatges and Philip Lupo, Baylor College of Medicine; Noha Sharafeldin and Smita Bhatia, University of Alabama at Birmingham; Achal Neupane, Jessica Baedke, Brian Lenny, Angela Delaney, Stephanie Dixon, Gregory Armstrong, Melissa Hudson, Kirsten Ness, Leslie Robison and Yutaka Yasui, all of St. Jude.

The study was supported by grants from the National Cancer Institute (R21 CA261833, R01 CA261898, R01 CA216354, U01 CA195547, U24 CA55727, CA21765), Children’s Cancer Research Fund and University of Minnesota Foundation Pediatric Scholar Award and ALSAC, the fundraising and awareness organization of St. Jude.