Association of germline variation with androgen ablation (AA) failure in advanced hormone-sensitive prostate cancer (HSPC).

Authors

null

Samith Thomas Kochuparambil

Mayo Clinic, Rochester, MN, Rochester, MN

Samith Thomas Kochuparambil , Ben Yiming Zhang , Shaun M. Riska , Douglas W. Mahoney , Shannon McDonnell , Adam M Lee , Fernando Quevedo , Brian Addis Costello , Henry Clement Pitot , Ricardo Ribeiro , Rui Medeiros , Catia Monteiro , Augusto Nogueira , Joaquina Mauricio , Avelino Manuel Fraga , Fernando Eduardo Calais Da Silva , James Robert Cerhan , Manish Kohli

Organizations

Mayo Clinic, Rochester, MN, Rochester, MN, Molecular Oncology Group - CI, Portuguese Institute of Oncology, Porto, Portugal, Research Department LPCC, Portuguese League Against Cancer, Porto, Portugal, Medical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal, Urology Department, Porto Hospital Centre, Sto Antonio Hospital, Porto, Portugal, Urology Department, Central Lisbon Hospital Centre, Lisbon, Portugal, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, Rochester, MN

Research Funding

No funding sources reported

Background: Predictive markers of response to AA are not known. In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 candidate hormone-related genes (JAK2, TRMT11, NKX3-1 and HSD17B12)were associated with response to AA in HSPC in a North American cohort of 519 subjects. We attempt to replicate these findings in a cohort of Portuguese patients. Methods: The Portuguese cohort consisted of 308 HSPC patients, and the primary endpoint was time to AA failure, defined as time from initiating continuous AA to two serial PSA increases over the nadir, initiation of chemotherapy for progressive disease, or clinical or imaging based progression, whichever came first. For each SNP, we calculated hazard ratios (HRs) and 95% confidence intervals (CI) for time to AA failure using a recessive model with adjustment for Gleason score (GS). Results: The median age of the Portuguese cohort was 69 years (range 43, 85). The GS distribution was 35% subjects with GS≥8; 35% with GS=7 and 30% with GS<7. Median time to AA failure for the cohort was 1.8 years (IQ range: 0.3, 3.6). Association of each SNP with time to AA failure is shown in the Table. None of the SNPs replicated. However, there was a suggestive inverse association for rs10503733 (NKX3.1) with time to AA failure (P=0.07). Conclusions: While we were not able to replicate our initial findings, there was an unexpected association with rs10503733 (NKX3.1 gene) that may warrant additional clinical validation.

SNPGeneDominant/
recessive
Recessive model
adjusted HR (95% CI)
Adjusted
P-value
rs9388462TRMT11232/670.85 (0.53-1.36)0.50
rs2295005TRMT11245/551.13 (0.68-1.86)0.64
rs1268121TRMT11294/090.93 (0.34-2.53)0.89
rs10503733NKX3-1281/170.27 (0.07-1.11)0.070
rs7005368NKX3-1304/02----
rs3808850JAK2275/260.81 (0.40-1.71)0.62
rs4372063JAK2258/410.87 (0.49-1.56)0.65
rs11037662HSD17B12297/072.41 (0.76-7.64)0.14

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2015 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session B: Prostate, Penile, Testicular, and Urethral Cancers, and Urothelial Carcinoma

Track

Urothelial Carcinoma,Prostate Cancer,Penile, Urethral, and Testicular Cancers

Sub Track

Prostate Cancer - Advanced Disease

Citation

J Clin Oncol 33, 2015 (suppl 7; abstr 209)

DOI

10.1200/jco.2015.33.7_suppl.209

Abstract #

209

Poster Bd #

B2

Abstract Disclosures

Similar Abstracts

First Author: Manish Kohli

First Author: Samith Thomas Kochuparambil

First Author: Alicia K. Morgans