 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 13, 2018 |
| Title |
Germline variant in SLCO2B1 and response to abiraterone acetate plus prednisone (AA) in new onset metastatic castration-resistant prostate cancer (mCRPC) |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
|
| Summary |
There are many treatment options available for men with metastatic castration-resistant prostate cancer (mCRPC). Yet, biomarkers predictive of differential response to treatment are currently available. A recent translational study suggested that SLCO2B1 genotype could predict response to abiraterone acetate (AA) for men with advanced prostate cancer. Here, we investigate whether germline variants in SLCO2B1 are predictive of response to first-line AA in men with new mCRPC. Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah. Genotyping was performed using the Illumina OmniExpress genotyping platform. Primary endpoint was progression-free survival (PFS) on first-line AA in men with mCRPC. We performed a pre-speciļ¬ed multivariate Cox regression analysis to assess the independent predictive value of rs12422149 and rs1789693 on PFS on AA. Of 401 men with advanced prostate cancer genotyped, 323 were homozygous wild type for rs12422149 (80.5%), 74 were heterozygous (18.5%), and 4 were homozygous variant (1.0%). In a multivariate analysis of 79 men treated with first-line AA for mCRPC, men heterozygous for rs12422149 had significantly improved median PFS compared to the homozygous wild-type group (8.9 months vs. 6.3 months, HR 0.46, 95% CI 0.23-0.94, p=0.03). No significant difference in median PFS was seen by rs1789693 genotype. In this first clinical validation of translational data reported by Mostaghel and colleagues, germline variant alleles in rs12422149 of SLCO2B1 are common and predict improved response to first-line AA In men with mCRPC.
|
| |
|
| Overall design |
In a multivariate analysis of 79 men treated with first-line AA for mCRPC, men heterozygous for rs12422149 had significantly improved median PFS compared to the homozygous wild-type group (8.9 months vs. 6.3 months, HR 0.46, 95% CI 0.23-0.94, p=0.03). No significant difference in median PFS was seen by rs1789693 genotype.
|
| |
|
| Contributor(s) |
Hahn AW, Gill DM, Poole A, Nussenzveig RH, Wilson S, Farnham JM, Stephenson RA, Cannon-Albright LA, Maughan BL, Agarwal N |
| Citation(s) |
30587554 |
| Submission date |
Dec 12, 2018 |
| Last update date |
Mar 14, 2019 |
| Contact name |
Roberto Henrique Nussenzveig |
| Organization name |
University of Utah/Huntsman Cancer Institute
|
| Department |
Oncology
|
| Street address |
2000 Circle of Hope
|
| City |
Salt Lake City |
| State/province |
Utah |
| ZIP/Postal code |
84101 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL21168 |
HumanOmniExpress-24 v1.0 BeadChip [SNP_ID version] |
| GPL22678 |
HumanOmniExpress-24 v1.1 BeadChip [SNP_ID version] |
| GPL25924 |
Infinium OmniExpress-24v1-2_A1 |
|
| Samples (79)
|
|
| Relations |
| BioProject |
PRJNA509610 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123695_Matrix_processed_GPL21168.txt.gz |
390.9 Mb |
(ftp)(http) |
TXT |
| GSE123695_Matrix_processed_GPL22678.txt.gz |
10.9 Mb |
(ftp)(http) |
TXT |
| GSE123695_Matrix_processed_GPL25924.txt.gz |
184.4 Mb |
(ftp)(http) |
TXT |
| GSE123695_Matrix_signal_intensities_GPL21168.txt.gz |
361.1 Mb |
(ftp)(http) |
TXT |
| GSE123695_Matrix_signal_intensities_GPL22678.txt.gz |
8.8 Mb |
(ftp)(http) |
TXT |
| GSE123695_Matrix_signal_intensities_GPL25924.txt.gz |
160.6 Mb |
(ftp)(http) |
TXT |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...