Baylor College of Medicine, Houston, TX, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Endocr Relat Cancer. 2024 Oct 29;31(12). doi: 10.1530/ERC-24-0195. Print 2024 Dec 1.
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.
激素治疗（HT）用于治疗前列腺癌据报道会引起身体成分的不良变化。临床上，患者之间的身体成分变化具有异质性，但导致身体成分毒性的生物学和临床决定因素尚不清楚。在此，我们检验了以下假说，即类固醇生成基因的遗传多态性与 HT 后身体成分的差异变化有关。患有生化复发前列腺癌（BCR）的男性，如果符合以下条件，则有资格接受 8 个月的 LHRH 类似物（LHRHa）+/-阿比特龙醋酸盐（AAP）治疗：i）治疗前后进行 L3 的 CT 成像；和 ii）采集有核细胞。回顾性提取心脏代谢合并症。使用基于人工智能的分割工具测量身体成分。进行全外显子或全基因组测序。在接受 8 个月 HT 治疗的 162 名男性中，骨骼肌质量（SMMi）中位数损失为 6.6%，皮下脂肪增加 12.3%。患有 2 型糖尿病的男性在治疗后 SMMi 损失更高（-11.1%比-6.3%，P=0.003）。对于 150 名具有种系 NGS 的男性，SRD5A2 rs523349 基因型与 HT 后骨骼肌密度的差异损失相关，（-1.3%比-7.1%，P=0.04）。此外，HSD3B1 rs104703 基因型与基线内脏脂肪组织减少相关（63.0 cm2/m2 比 77.9，P=0.05）。在患有 BCR 的男性中，HT 导致明显的骨骼肌损失和皮下脂肪增加。SRD5A2 和 T2DM 的遗传多态性与骨骼肌毒性的差异有关。这些发现表明，遗传多态性可能导致 HT 观察到的身体成分毒性。
