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Genome-wide association study of prostate cancer-specific survival.

ABSTRACT: BACKGROUND:Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS:We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). RESULTS:We observed no significant association between genetic variants and prostate cancer survival. CONCLUSIONS:Common genetic variants with large impact on prostate cancer survival were not observed in this study. IMPACT:Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

SUBMITTER: Szulkin R

PROVIDER: S-EPMC5674990 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Genome-wide association study of prostate cancer-specific survival.

Szulkin Robert R Karlsson Robert R Whitington Thomas T Aly Markus M Gronberg Henrik H Eeles Rosalind A RA Easton Douglas F DF Kote-Jarai Zsofia Z Al Olama Ali Amin AA Benlloch Sara S Muir Kenneth K Giles Graham G GG Southey Melissa C MC FitzGerald Liesel M LM Henderson Brian E BE Schumacher Fredrick R FR Haiman Christopher A CA Sipeky Csilla C Tammela Teuvo L J TL Nordestgaard Børge G BG Key Timothy J TJ Travis Ruth C RC Neal David E DE Donovan Jenny L JL Hamdy Freddie C FC Pharoah Paul D P PD Pashayan Nora N Khaw Kay-Tee KT Stanford Janet L JL Thibodeau Stephen N SN McDonnell Shannon K SK Schaid Daniel J DJ Maier Christiane C Vogel Walther W Luedeke Manuel M Herkommer Kathleen K Kibel Adam S AS Cybulski Cezary C Lubiński Jan J Kluźniak Wojciech W Cannon-Albright Lisa L Brenner Hermann H Herrmann Volker V Holleczek Bernd B Park Jong Y JY Sellers Thomas A TA Lim Hui-Yi HY Slavov Chavdar C Kaneva Radka P RP Mitev Vanio I VI Spurdle Amanda A Teixeira Manuel R MR Paulo Paula P Maia Sofia S Pandha Hardev H Michael Agnieszka A Kierzek Andrzej A Batra Jyotsna J Batra Jyotsna J Clements Judith A JA Albanes Demetrius D Andriole Gerald L GL Berndt Sonja I SI Chanock Stephen S Gapstur Susan M SM Giovannucci Edward L EL Hunter David J DJ Kraft Peter P Le Marchand Loic L Ma Jing J Mondul Alison M AM Penney Kathryn L KL Stampfer Meir J MJ Stevens Victoria L VL Weinstein Stephanie J SJ Trichopoulou Antonia A Bueno-de-Mesquita Bas H BH Tjønneland Anne A Cox David G DG Maehle Lovise L Schleutker Johanna J Lindström Sara S Wiklund Fredrik F

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20150825 11

<h4>Background</h4>Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.<h4>Methods</h4>We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).<h4>Results</h4>W ...[more]

PMID: 26307654

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Project description:BackgroundEstimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer.MethodsThe authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts.ResultsA total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort.ConclusionsThe authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making.Lay summaryThis article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

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Genome-wide association study of prostate cancer-specific survival.

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Genome-wide association study of prostate cancer-specific survival.

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