GWAS from a multicenter prospective study of radium-223 in bone-metastatic castration-resistant prostate cancer.
Tanegashima T, Shiota M, Doi A, Tatarano S, Kamba T, Igawa T (+11 more)
Abstract
BackgroundRadium-223 dichloride improves survival and delays symptomatic skeletal events in patients with bone-metastatic castration-resistant prostate cancer; however, therapeutic responses vary considerably among individuals, and predictive germline biomarkers remain undefined. We conducted a prospective multicenter genome-wide association study within the KYUCOG-1901 cohort to identify germline single-nucleotide polymorphisms associated with the clinical efficacy of radium-223.ResultsAmong 93 patients with bone-predominant castration-resistant prostate cancer treated with up to six cycles of radium-223, the intronic variant rs1568679 in MEIS2 reached genome-wide significance for association with ≥ 30% decline in prostate-specific antigen (P ConclusionsThe germline variant rs1568679 in MEIS2 may represent a potential biomarker associated with favorable response to radium-223 in metastatic castration-resistant prostate cancer. These findings suggest that MEIS2-related DNA repair regulation may influence susceptibility to α-particle-induced cytotoxicity and may facilitate biomarker-driven treatment strategies for optimizing Ra-223 therapy.Trial registrationUniversity Hospital Medical Information Network (UMIN), UMIN000040358, registered 11 May 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045641 .