Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer

Indu Kohaar; Patricia Porter-Gill; Petra Lenz; Yi Ping Fu; Adam Mumy; Wei Tang; Andrea B. Apolo; Nathaniel Rothman; Dalsu Baris; Alan R. Schned; Kris Ylaya; Molly Schwenn; Alison Johnson; Michael Jones; Masatoshi Kida; Debra T. Silverman; Stephen M. Hewitt; Lee E. Moore; Ludmila Prokunina-Olsson

doi:10.1093/jnci/djs458

Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer

Indu Kohaar
, Patricia Porter-Gill
, Petra Lenz
, Yi Ping Fu
, Adam Mumy
, Wei Tang
, Andrea B. Apolo
, Nathaniel Rothman
, Dalsu Baris
, Alan R. Schned
, Kris Ylaya
, Molly Schwenn
, Alison Johnson
, Michael Jones
, Masatoshi Kida
, Debra T. Silverman
, Stephen M. Hewitt
, Lee E. Moore
, Ludmila Prokunina-Olsson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	69-73
Number of pages	5
Journal	Journal of the National Cancer Institute
Volume	105
Issue number	1
DOIs	https://doi.org/10.1093/jnci/djs458
State	Published - 2 Jan 2013
Externally published	Yes

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Kohaar, I., Porter-Gill, P., Lenz, P., Fu, Y. P., Mumy, A., Tang, W., Apolo, A. B., Rothman, N., Baris, D., Schned, A. R., Ylaya, K., Schwenn, M., Johnson, A., Jones, M., Kida, M., Silverman, D. T., Hewitt, S. M., Moore, L. E., & Prokunina-Olsson, L. (2013). Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer. Journal of the National Cancer Institute, 105(1), 69-73. https://doi.org/10.1093/jnci/djs458

@article{31d756e34faf4520b8fd2f85b82b0336,

title = "Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer",

abstract = "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{\texttimes}10-11; n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10{\texttimes}10-5; n = 173) and T1 (P = 2.64{\texttimes}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.",

author = "Indu Kohaar and Patricia Porter-Gill and Petra Lenz and Fu, \{Yi Ping\} and Adam Mumy and Wei Tang and Apolo, \{Andrea B.\} and Nathaniel Rothman and Dalsu Baris and Schned, \{Alan R.\} and Kris Ylaya and Molly Schwenn and Alison Johnson and Michael Jones and Masatoshi Kida and Silverman, \{Debra T.\} and Hewitt, \{Stephen M.\} and Moore, \{Lee E.\} and Ludmila Prokunina-Olsson",

note = "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{\textquoteright}s Career Development Award (to Y-PF).",

year = "2013",

month = jan,

day = "2",

doi = "10.1093/jnci/djs458",

language = "English",

volume = "105",

pages = "69--73",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

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}

Kohaar, I, Porter-Gill, P, Lenz, P, Fu, YP, Mumy, A, Tang, W, Apolo, AB, Rothman, N, Baris, D, Schned, AR, Ylaya, K, Schwenn, M, Johnson, A, Jones, M, Kida, M, Silverman, DT, Hewitt, SM, Moore, LE & Prokunina-Olsson, L 2013, 'Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer', Journal of the National Cancer Institute, vol. 105, no. 1, pp. 69-73. https://doi.org/10.1093/jnci/djs458

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 - https://www.scopus.com/pages/publications/84871942874

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 -

Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer

Abstract

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