Genetic Variants in CASP3, BMP5, and IRS2 Genes May Influence Survival in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy

被引：33

作者：

Huang, Shu-Pin ^{[1
,2
,3
]}

Bao, Bo-Ying ^{[4
,5
]}

Hour, Tzyh-Chyuan ^{[6
]}

Huang, Chao-Yuan ^{[7
]}

Yu, Chia-Cheng ^{[8
]}

Liu, Chia-Chu ^{[1
,2
]}

Lee, Yung-Chin ^{[1
,2
]}

Huang, Chun-Nung ^{[1
,2
]}

Pao, Jiunn-Bey ^{[9
]}

Huang, Chun-Hsiung ^{[1
,2
]}

机构：

[1] Kaohsiung Med Univ Hosp, Dept Urol, Kaohsiung, Taiwan

[2] Kaohsiung Med Univ, Coll Med, Fac Med, Dept Urol, Kaohsiung, Taiwan

[3] Kaohsiung Med Univ Hosp, Ctr Canc, Kaohsiung, Taiwan

[4] China Med Univ, Dept Pharm, Taichung, Taiwan

[5] China Med Univ Hosp, Sex Hormone Res Ctr, Taichung, Taiwan

[6] Kaohsiung Med Univ, Inst Biochem, Kaohsiung, Taiwan

[7] Natl Taiwan Univ Hosp, Dept Urol, Taipei, Taiwan

[8] Kaohsiung Vet Gen Hosp, Dept Surg, Div Urol, Kaohsiung, Taiwan

[9] Taipei City Hosp, Yangming Branch, Dept Pharm, Taipei, Taiwan

来源：

PLOS ONE | 2012年 / 7卷 / 07期

关键词：

GENOME-WIDE ASSOCIATION; INSULIN-RECEPTOR SUBSTRATE-1; SUSCEPTIBILITY LOCI; INCREASED EXPRESSION; MULTIPLE LOCI; IDENTIFICATION; POLYMORPHISMS; MORTALITY;

D O I：

10.1371/journal.pone.0041219

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Several genome-wide association studies (GWAS) have been conducted to identify the common single nucleotide polymorphisms (SNPs) that influence the risk of prostate cancer. It was hypothesized that some prostate cancer-associated SNPs might relate to the clinical outcomes in patients treated for prostate cancer using androgen-deprivation therapy (ADT). A cohort of 601 patients who have received ADT for prostate cancer was genotyped for 29 SNPs that have been associated with prostate cancer in Cancer Genetic Markers of Susceptibility GWAS, and within the genes that have been implicated in cancer. Prognostic significance of these SNPs on the disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model. Three SNPs, namely CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346, were found to be closely associated with the ACM (P <= 0.042), and BMP5 rs3734444 and IRS2 rs7986346 were also noted to be significantly related to the PCSM (P <= 0.032) after adjusting for the known clinicopathologic predictors. Moreover, patients carrying a greater number of unfavorable genotypes at the loci of interest had a shorter time to ACM and PCSM during ADT (P for trend <0.001). Our results suggest that CASP3 rs4862396, BMP5 rs3734444 and IRS2 rs7986346 may affect the survival in patients after ADT for prostate cancer, and the analysis of these SNPs can help identify patients at higher risk of poor outcome.

引用

页数：7

共 39 条

[1] Multiple loci on 8q24 associated with prostate cancer susceptibility [J].

Al Olama, Ali Amin ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Guy, Michelle ;

Morrison, Jonathan ;

Severi, Gianluca ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Jhavar, Sameer ;

Saunders, Ed ;

Hopper, John L. ;

Southey, Melissa C. ;

Muir, Kenneth R. ;

English, Dallas R. ;

Dearnaley, David P. ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Wilkinson, Rosemary A. ;

Sawyer, Emma ;

Lophatananon, Artitaya ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Cooper, Colin ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Neal, David E. ;

Eeles, Rosalind A. ;

Easton, Douglas F. .

NATURE GENETICS, 2009, 41 (10) :1058-1060

[2] Significant associations of prostate cancer susceptibility variants with survival in patients treated with androgen-deprivation therapy [J].

Bao, Bo-Ying ;

Pao, Jiunn-Bey ;

Huang, Chun-Nung ;

Pu, Yeong-Shiau ;

Chang, Ta-Yuan ;

Lan, Yu-Hsuan ;

Lu, Te-Ling ;

Lee, Hong-Zin ;

Chen, Lu-Min ;

Ting, Wen-Chien ;

Hsieh, Chi-Jeng ;

Huang, Shu-Pin .

INTERNATIONAL JOURNAL OF CANCER, 2012, 130 (04) :876-884

[3] Polymorphisms inside MicroRNAs and MicroRNA Target Sites Predict Clinical Outcomes in Prostate Cancer Patients Receiving Androgen-Deprivation Therapy [J].

Bao, Bo-Ying ;

Pao, Jiunn-Bey ;

Huang, Chun-Nung ;

Pu, Yeong-Shiau ;

Chang, Ta-Yuan ;

Lan, Yu-Hsuan ;

Lu, Te-Ling ;

Lee, Hong-Zin ;

Juang, Shin-Hun ;

Chen, Lu-Min ;

Hsieh, Chi-Jeng ;

Huang, Shu-Pin .

CLINICAL CANCER RESEARCH, 2011, 17 (04) :928-936

[4] EXPRESSION OF BONE MORPHOGENETIC PROTEINS IN HUMAN PROSTATIC ADENOCARCINOMA AND BENIGN PROSTATIC HYPERPLASIA [J].

BENTLEY, H ;

HAMDY, FC ;

HART, KA ;

SEID, JM ;

WILLIAMS, JL ;

JOHNSTONE, D ;

RUSSELL, RGG .

BRITISH JOURNAL OF CANCER, 1992, 66 (06) :1159-1163

[5] Increased expression of insulin receptor substrate-1 in human pancreatic cancer [J].

Bergmann, U ;

Funatomi, H ;

Kornmann, M ;

Beger, HG ;

Korc, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 220 (03) :886-890

[6] Cell- and gene-specific regulation of primary target genes by the androgen receptor [J].

Bolton, Eric C. ;

So, Alex Y. ;

Chaivorapol, Christina ;

Haqq, Christopher M. ;

Li, Hao ;

Yamamoto, Keith R. .

GENES & DEVELOPMENT, 2007, 21 (16) :2005-2017

[7]

Chang Q, 2002, CANCER RES, V62, P6035

[8] Bone morphogenic factor gene dosage abnormalities in prostatic intraepithelial neoplasia and prostate cancer [J].

Doak, Shareen H. ;

Jenkins, Spencer A. ;

Hurle, Rhidian A. ;

Varma, Murali ;

Hawizy, Azad ;

Kynaston, Howard G. ;

Parry, James M. .

CANCER GENETICS AND CYTOGENETICS, 2007, 176 (02) :161-165

[9] Multiple newly identified loci associated with prostate cancer susceptibility [J].

Eeles, Rosalind A. ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Al Olama, Ali Amin ;

Guy, Michelle ;

Jugurnauth, Sarah K. ;

Mulholland, Shani ;

Leongamornlert, Daniel A. ;

Edwards, Stephen M. ;

Morrison, Jonathan ;

Field, Helen I. ;

Southey, Melissa C. ;

Severi, Gianluca ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Dearnaley, David P. ;

Muir, Kenneth R. ;

Smith, Charmaine ;

Bagnato, Melisa ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Gehr-Swain, Beatrice N. ;

Wilkinson, Rosemary A. ;

Cox, Angie ;

Lewis, Sarah ;

Brown, Paul M. ;

Jhavar, Sameer G. ;

Tymrakiewicz, Malgorzata ;

Lophatananon, Artitaya ;

Bryant, Sarah L. ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Fisher, Cyril ;

Jamieson, Charles ;

Cooper, Colin S. ;

English, Dallas R. ;

Hopper, John L. ;

Neal, David E. ;

Easton, Douglas F. .

NATURE GENETICS, 2008, 40 (03) :316-321

[10] Identification of seven new prostate cancer susceptibility loci through a genome-wide association study [J].

Eeles, Rosalind A. ;

Kote-Jarai, Zsofia ;

Al Olama, Ali Amin ;

Giles, Graham G. ;

Guy, Michelle ;

Severi, Gianluca ;

Muir, Kenneth ;

Hopper, John L. ;

Henderson, Brian E. ;

Haiman, Christopher A. ;

Schleutker, Johanna ;

Hamdy, Freddie C. ;

Neal, David E. ;

Donovan, Jenny L. ;

Stanford, Janet L. ;

Ostrander, Elaine A. ;

Ingles, Sue A. ;

John, Esther M. ;

Thibodeau, Stephen N. ;

Schaid, Daniel ;

Park, Jong Y. ;

Spurdle, Amanda ;

Clements, Judith ;

Dickinson, Joanne L. ;

Maier, Christiane ;

Vogel, Walther ;

Doerk, Thilo ;

Rebbeck, Timothy R. ;

Cooney, Kathleen A. ;

Cannon-Albright, Lisa ;

Chappuis, Pierre O. ;

Hutter, Pierre ;

Zeegers, Maurice ;

Kaneva, Radka ;

Zhang, Hong-Wei ;

Lu, Yong-Jie ;

Foulkes, William D. ;

English, Dallas R. ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Morrison, Jonathan ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Wilkinson, Rosemary A. ;

Saunders, Edward J. ;

Page, Elizabeth C. ;

Sawyer, Emma J. ;

Edwards, Stephen M. ;

Dearnaley, David P. .

NATURE GENETICS, 2009, 41 (10) :1116-U97

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