المؤلفون: Pagadala, Meghana S, Lynch, Julie, Karunamuni, Roshan, Alba, Patrick R, Lee, Kyung Min, Agiri, Fatai Y, Anglin, Tori, Carter, Hannah, Gaziano, J Michael, Jasuja, Guneet Kaur, Deka, Rishi, Rose, Brent S, Panizzon, Matthew S, Hauger, Richard L, Seibert, Tyler M

المصدر: Journal of the National Cancer Institute. 115(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Prostate Cancer, Cancer, Urologic Diseases, Clinical Research, Genetics, Aging, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Humans, Male, Aged, Prostatic Neoplasms, Veterans, Retrospective Studies, Prostate-Specific Antigen, Cohort Studies, Early Detection of Cancer, Oncology & Carcinogenesis, Oncology and carcinogenesis

الوصف: BackgroundGenetic scores may provide an objective measure of prostate cancer risk and thus inform screening decisions. We evaluated whether a polygenic hazard score based on 290 genetic variants (PHS290) is associated with prostate cancer risk in a diverse population, including Black men, who have higher average risk of prostate cancer death but are often treated as a homogeneously high-risk group.MethodsThis was a retrospective analysis of the Million Veteran Program, a national, population-based cohort study of US military veterans conducted 2011-2021. Cox proportional hazards analyses tested for association of genetic and other risk factors (including self-reported race and ethnicity and family history) with age at death from prostate cancer, age at diagnosis of metastatic (nodal or distant) prostate cancer, and age at diagnosis of any prostate cancer.ResultsA total of 590 750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (P

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الوصول الحر: https://escholarship.org/uc/item/3sz039dxTest

المؤلفون: Zhong, Allison Y, Digma, Leonardino A, Hussain, Troy, Feng, Christine H, Conlin, Christopher C, Tye, Karen, Lui, Asona J, Andreassen, Maren MS, Rodríguez-Soto, Ana E, Karunamuni, Roshan, Kuperman, Joshua, Kane, Christopher J, Rakow-Penner, Rebecca, Hahn, Michael E, Dale, Anders M, Seibert, Tyler M

مصطلحات موضوعية: Cancer, Diffusion magnetic resonance imaging, Prostate, Quantitative magnetic resonance imaging, Restriction spectrum imaging, Urologic Diseases, Clinical Research, Prostate Cancer, Aging, Biomedical Imaging, Diffusion magnetic resonance, imaging, Quantitative magnetic resonance

الوصف: BackgroundMultiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs).ObjectiveTo evaluate RSIrs for automated patient-level detection of csPCa.Design setting and participantsWe retrospectively studied all patients (n = 151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI.InterventionWe calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records.Outcome measurements and statistical analysisWe compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α = 0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones.Results and limitationsAUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8sh387k2Test

المؤلفون: Huynh-Le, Minh-Phuong, Karunamuni, Roshan, Fan, Chun Chieh, Asona, Lui, Thompson, Wesley K, Martinez, Maria Elena, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth R, Lophatananon, Artitaya, Schleutker, Johanna, Pashayan, Nora, Batra, Jyotsna, Grönberg, Henrik, Neal, David E, Nordestgaard, Børge G, Tangen, Catherine M, MacInnis, Robert J, Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A, Travis, Ruth C, Blot, William J, Stanford, Janet L, Mucci, Lorelei A, West, Catharine ML, Nielsen, Sune F, Kibel, Adam S, Cussenot, Olivier, Berndt, Sonja I, Koutros, Stella, Sørensen, Karina Dalsgaard, Cybulski, Cezary, Grindedal, Eli Marie, Menegaux, Florence, Park, Jong Y, Ingles, Sue A, Maier, Christiane, Hamilton, Robert J, Rosenstein, Barry S, Lu, Yong-Jie, Watya, Stephen, Vega, Ana, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L, Huff, Chad D, Teixeira, Manuel R, Multigner, Luc, Leach, Robin J, Brenner, Hermann, John, Esther M, Kaneva, Radka, Logothetis, Christopher J, Neuhausen, Susan L, De Ruyck, Kim, Ost, Piet, Razack, Azad, Newcomb, Lisa F, Fowke, Jay H, Gamulin, Marija, Abraham, Aswin, Claessens, Frank, Castelao, Jose Esteban, Townsend, Paul A, Crawford, Dana C, Petrovics, Gyorgy, van Schaik, Ron HN, Parent, Marie-Élise, Hu, Jennifer J, Zheng, Wei, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M

المصدر: Prostate Cancer and Prostatic Diseases. 25(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Prostate Cancer, Cancer, Urologic Diseases, Prevention, Genetics, Good Health and Well Being, Male, Humans, Prostate-Specific Antigen, Prostatic Neoplasms, Early Detection of Cancer, Polymorphism, Single Nucleotide, Risk Factors, Risk Assessment, Genetic Predisposition to Disease, UKGPCS collaborators, APCB, NC-LA PCaP Investigators, IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, Profile Study Steering Committee, PRACTICAL Consortium, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis

الوصف: BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

الوصول الحر: https://escholarship.org/uc/item/00p470cnTest

المؤلفون: Karunamuni, Roshan A, Huynh-Le, Minh-Phuong, Fan, Chun C, Thompson, Wesley, Lui, Asona, Martinez, Maria Elena, Rose, Brent S, Mahal, Brandon, Eeles, Rosalind A, Kote-Jarai, Zsofia, Muir, Kenneth, Lophatananon, Artitaya, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Blot, William J, Zheng, Wei, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Park, Jong Y, Lin, Hui-Yi, Taylor, Jack A, Bensen, Jeannette T, Mohler, James L, Fontham, Elizabeth TH, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Romana, Marc, Leach, Robin J, John, Esther M, Fowke, Jay H, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Cullen, Jennifer, Petrovics, Gyorgy, Parent, Marie-Élise, Hu, Jennifer J, Sanderson, Maureen, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M

المصدر: Prostate Cancer and Prostatic Diseases. 25(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prostate Cancer, Prevention, Genetics, Cancer, Urologic Diseases, Black People, Case-Control Studies, Chromosomes, Human, Pair 8, Genetic Predisposition to Disease, Humans, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Assessment, White People, UKGPCS Collaborators, PRACTICAL Consortium, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis

الوصف: BackgroundWe previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.Materials and methodsGenotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.ResultsCF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.ConclusionWe identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.

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الوصول الحر: https://escholarship.org/uc/item/73k820f8Test

المؤلفون: Garcia-Ruiz, Alonso, Pons-Escoda, Albert, Grussu, Francesco, Naval-Baudin, Pablo, Monreal-Aguero, Camilo, Hermann, Gretchen, Karunamuni, Roshan, Ligero, Marta, Lopez-Rueda, Antonio, Oleaga, Laura, Berbís, M. Álvaro, Cabrera-Zubizarreta, Alberto, Martin-Noguerol, Teodoro, Luna, Antonio, Seibert, Tyler M., Majos, Carlos, Perez-Lopez, Raquel

المساهمون: Prostate Cancer Foundation, Instituto de Salud Carlos III

المصدر: Cell Reports Medicine ; volume 5, issue 3, page 101464 ; ISSN 2666-3791

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.xcrm.2024.101464Test
https://api.elsevier.com/content/article/PII:S2666379124001083?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666379124001083?httpAccept=text/plainTest

المؤلفون: Simon, Aaron B, Hurt, Brian, Karunamuni, Roshan, Kim, Gwe-Ya, Moiseenko, Vitali, Olson, Scott, Farid, Nikdokht, Hsiao, Albert, Hattangadi-Gluth, Jona A

المصدر: Scientific Reports. 12(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Biomedical Imaging, Clinical Research, Neurosciences, Neurological, Cerebral Angiography, Cerebral Arteries, Cerebral Veins, Deep Learning, Humans, Intracranial Arteriovenous Malformations, Magnetic Resonance Angiography, Multiparametric Magnetic Resonance Imaging, Radiosurgery

الوصف: Stereotactic radiosurgery planning for cerebral arteriovenous malformations (AVM) is complicated by the variability in appearance of an AVM nidus across different imaging modalities. We developed a deep learning approach to automatically segment cerebrovascular-anatomical maps from multiple high-resolution magnetic resonance imaging/angiography (MRI/MRA) sequences in AVM patients, with the goal of facilitating target delineation. Twenty-three AVM patients who were evaluated for radiosurgery and underwent multi-parametric MRI/MRA were included. A hybrid semi-automated and manual approach was used to label MRI/MRAs with arteries, veins, brain parenchyma, cerebral spinal fluid (CSF), and embolized vessels. Next, these labels were used to train a convolutional neural network to perform this task. Imaging from 17 patients (6362 image slices) was used for training, and 6 patients (1224 slices) for validation. Performance was evaluated by Dice Similarity Coefficient (DSC). Classification performance was good for arteries, veins, brain parenchyma, and CSF, with DSCs of 0.86, 0.91, 0.98, and 0.91, respectively in the validation image set. Performance was lower for embolized vessels, with a DSC of 0.75. This demonstrates the proof of principle that accurate, high-resolution cerebrovascular-anatomical maps can be generated from multiparametric MRI/MRA. Clinical validation of their utility in radiosurgery planning is warranted.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5pn0g8ktTest

المؤلفون: Pihlstrøm, Lasse, Fan, Chun C, Frei, Oleksandr, Tan, Manuela, Karunamuni, Roshan A, Blauwendraat, Cornelis, Bandres‐Ciga, Sara, Gan‐Or, Ziv, Grosset, Donald G, Consortium, International Parkinson's Disease Genomics, Dale, Anders M, Seibert, Tyler M, Andreassen, Ole A

المصدر: Movement Disorders. 37(1)

مصطلحات موضوعية: Neurodegenerative, Aging, Brain Disorders, Neurosciences, Prevention, Patient Safety, Parkinson's Disease, Detection, screening and diagnosis, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Biomarkers, Humans, Incidence, Multifactorial Inheritance, Parkinson Disease, Risk Factors, Parkinson's disease, age at onset, genetics, polygenic score, prediction, International Parkinson's Disease Genomics Consortium, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery

الوصف: BackgroundParkinson's disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders.ObjectivesWe aimed to develop and validate a polygenic hazard score model in sporadic PD.MethodsUsing a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls.ResultsA polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups.ConclusionsWe demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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الوصول الحر: https://escholarship.org/uc/item/6j76s343Test

المؤلفون: Digma, Leonardino A, Feng, Christine H, Conlin, Christopher C, Rodríguez-Soto, Ana E, Zhong, Allison Y, Hussain, Troy S, Lui, Asona J, Batra, Kanha, Simon, Aaron B, Karunamuni, Roshan, Kuperman, Joshua, Rakow-Penner, Rebecca, Hahn, Michael E, Dale, Anders M, Seibert, Tyler M

المصدر: Scientific Reports. 12(1)

مصطلحات موضوعية: Physical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Cancer, Bioengineering, Biomedical Imaging, Artifacts, Bone Neoplasms, Diffusion Magnetic Resonance Imaging, Humans, Image Interpretation, Computer-Assisted, Male, Predictive Value of Tests, Prospective Studies, Prostatic Neoplasms, Reproducibility of Results, Whole Body Imaging

الوصف: Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T2-weighted images were annotated. Changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p

الوصول الحر: https://escholarship.org/uc/item/1c68h01hTest

المؤلفون: Pihlstrøm, Lasse, Fan, Chun C, Frei, Oleksandr, Tan, Manuela, Karunamuni, Roshan A, Blauwendraat, Cornelis, Bandres-Ciga, Sara, Gan-Or, Ziv, Grosset, Donald G, International Parkinson's Disease Genomics Consortium (IPDGC), Dale, Anders M, Seibert, Tyler M, Andreassen, Ole A

مصطلحات موضوعية: International Parkinson's Disease Genomics Consortium, Parkinson's disease, age at onset, genetics, polygenic score, prediction, Neurodegenerative, Prevention, Aging, Parkinson's Disease, Neurosciences, Patient Safety, Brain Disorders, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences

الوصف: BackgroundParkinson's disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders.ObjectivesWe aimed to develop and validate a polygenic hazard score model in sporadic PD.MethodsUsing a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls.ResultsA polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups.ConclusionsWe demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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الوصول الحر: https://escholarship.org/uc/item/6j76s343Test

المؤلفون: Huynh-Le, Minh-Phuong, Karunamuni, Roshan, Fan, Chun Chieh, Thompson, Wesley K, Muir, Kenneth, Lophatananon, Artitaya, Tye, Karen, Wolk, Alicja, Håkansson, Niclas, Mills, Ian G, Andreassen, Ole A, Dale, Anders M, Seibert, Tyler M

المصدر: Prostate Cancer and Prostatic Diseases. 24(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Urologic Diseases, Cancer, Prevention, Aging, Clinical Research, Prostate Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Aged, 80 and over, Biomarkers, Tumor, Case-Control Studies, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Prognosis, Prostatic Neoplasms, Survival Rate, Sweden, PRACTICAL Consortium, Urology & Nephrology, Clinical sciences, Oncology and carcinogenesis

الوصف: BackgroundClinical variables-age, family history, genetics-are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated if adding PHS to clinical variables improves associations with prostate cancer death.MethodsGenotype/phenotype data were obtained from a nested case-control Cohort of Swedish Men (n = 3279; 2163 with prostate cancer, 278 prostate cancer deaths). PHS and clinical variables (family history, alcohol intake, smoking, heart disease, hypertension, diabetes, body mass index) were tested via univariable Cox proportional hazards models for association with age at prostate cancer death. Multivariable Cox models with/without PHS were compared with log-likelihood tests.ResultsMedian age at last follow-up/prostate cancer death was 78.0 (IQR: 72.3-84.1) and 81.4 (75.4-86.3) years, respectively. On univariable analysis, PHS46 (HR 3.41 [95% CI 2.78-4.17]), family history (HR 1.72 [1.46-2.03]), alcohol (HR 1.74 [1.40-2.15]), diabetes (HR 0.53 [0.37-0.75]) were each associated with prostate cancer death. On multivariable analysis, PHS46 (HR 2.45 [1.99-2.97]), family history (HR 1.73 [1.48-2.03]), alcohol (HR 1.45 [1.19-1.76]), diabetes (HR 0.62 [0.42-0.90]) all remained associated with fatal disease. Including PHS46 or PHS166 improved multivariable models for fatal prostate cancer (p

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الوصول الحر: https://escholarship.org/uc/item/4255d4t4Test