Genetic Markers of Early Skeletal Muscle Loss in Adolescent and Young Adult Cancer Patients Treated with Anthracyclines

Vollständiger Abstract

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Purpose: Skeletal muscle (SM) loss occurs during early anthracycline treatment in adolescent and young adult (AYA) cancer patients. Identifying those at greatest risk is critical for prevention. This study aimed to determine if genetic variants previously associated with SM loss in the general population are also associated with SM loss in AYA cancer patients receiving anthracycline chemotherapy. Methods: SM change was quantified via computed tomography for 138 AYA cancer patients. The genome-wide association studies (GWAS) catalog was queried to identify candidate variants associated with SM index (SMI) or sarcopenia. Of the 18 GWAS-implicated variants, genotyping data were available in the study population for nine. Multivariable logistic regression was performed for each variant and risk of SM loss at the end of treatment and 1-year follow-up with adjustment for anthracycline dose, radiation exposure, diagnosis, sex, age, and follow-up time. Results: The T allele of rs97384 (chr11:61624181) located in the fatty acid desaturase 2 ( FADS2 ) gene was associated with risk of SM loss with a significant association for SM density (SMD) at follow-up (odds ratio: 2.37, 95% confidence interval: 1.27–4.45, p = 0.007). This variant was also borderline significant ( p < 0.10) for SMD at baseline and SMI at follow-up. Integration of other variants within the FADS2 region identified several loci with more significant associations with SM loss in our patient population than that conferred by rs97384. Conclusion: Genetic variants previously associated with SM loss in the general population were significantly associated with SMD reduction post-anthracycline treatment in AYAs. Thus, providing the possibility of SM loss risk assessment in this high-risk patient population.