TY - JOUR
T1 - Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer
AU - Kohaar, Indu
AU - Porter-Gill, Patricia
AU - Lenz, Petra
AU - Fu, Yi Ping
AU - Mumy, Adam
AU - Tang, Wei
AU - Apolo, Andrea B.
AU - Rothman, Nathaniel
AU - Baris, Dalsu
AU - Schned, Alan R.
AU - Ylaya, Kris
AU - Schwenn, Molly
AU - Johnson, Alison
AU - Jones, Michael
AU - Kida, Masatoshi
AU - Silverman, Debra T.
AU - Hewitt, Stephen M.
AU - Moore, Lee E.
AU - Prokunina-Olsson, Ludmila
N1 - Funding Information:
This work was supported in whole or in part with federal funds from the Intramural Research Program of the National Institutes of Health, National Cancer Institute (contract HHSN261200800001E). The New England Bladder Cancer study, the National Cancer Institute bladder cancer genome-wide association studies, and follow-up studies are supported by the Division of Cancer Epidemiology and Genetics, Intramural Research Program of the National Institutes of Health, National Cancer Institute. The New England Bladder Cancer study is also supported by a National Cancer Institute contract (NCI N02-CP-01037). This work was supported by a National Cancer Institute Director’s Career Development Award (to Y-PF).
PY - 2013/1/2
Y1 - 2013/1/2
N2 - A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10-11; n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10-5; n = 173) and T1 (P = 2.64×10-5; n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.
AB - A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10-11; n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10-5; n = 173) and T1 (P = 2.64×10-5; n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.
UR - http://www.scopus.com/inward/record.url?scp=84871942874&partnerID=8YFLogxK
U2 - 10.1093/jnci/djs458
DO - 10.1093/jnci/djs458
M3 - Article
C2 - 23266392
AN - SCOPUS:84871942874
SN - 0027-8874
VL - 105
SP - 69
EP - 73
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 1
ER -