Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Autor: Venkatesh N; Baylor College of Medicine, Houston, TX, USA., Tidwell RS; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Yu Y; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Aparicio A; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zurita AJ; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Subudhi SK; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Siddiqui BA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Mukhida SS; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gregg JR; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Corn PG; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Koutroumpakis E; Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., McQuade JL; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Frigo DE; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pilie PG; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Huff C; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Logothetis CJ; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hahn AW; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Endocrine-related cancer [Endocr Relat Cancer] 2024 Oct 29; Vol. 31 (12). Date of Electronic Publication: 2024 Oct 29 (Print Publication: 2024).
DOI: 10.1530/ERC-24-0195
Abstrakt: Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: i) CT imaging of L3 prior to and after treatment; and ii) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher losses of SMMi after treatment (-11.1% vs -6.3%, P = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs -7.1%, P = 0.04). In addition, the HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs 77.9, P = 0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM was associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.
Databáze: MEDLINE