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Influence of age on predictiveness of genetic risk score for prostate cancer in a Chinese hospital-based biopsy cohort.

ABSTRACT: We investigated whether age influences the predictiveness of genetic risk score (GRS) for prostate cancer (PCa) in a Chinese hospital-based biopsy cohort.We included consecutive patients who underwent prostate biopsies in two tertiary centers between 2012 and 2014. GRS was calculated using 24 PCa-associated genetic variants and its predictiveness was assessed by area under curve (AUC).Of 1120 men tested, 724 with prostate-specific antigen (PSA) < 20 ng/ml were selected for further analysis. Patients were divided into 3 groups by age cutoffs at 60 and 70 years. GRS significantly predicted PCa for all patients (AUC: 0.561; 95% CI: 0.514-0.609) and was an independent predictor in multivariate analysis for the 60-70 year-olds (AUC: 0.612, 95% CI: 0.541-0.684), but not for patients aged < 60 years or ? 70 years. For PCa with Gleason score ? 7, GRS discriminative ability was 0.582 (95% CI=0.527-0.637) for all patients, and 0.647 (95% CI: 0.541-0.684) for the 60-70 year-old group.GRS significantly increased clinical prediction of PCa and high-grade disease in Chinese men aged 60-70 years, which implies that men in this age group would benefit most from genetic testing.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC4673214 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Influence of age on predictiveness of genetic risk score for prostate cancer in a Chinese hospital-based biopsy cohort.

Zhu Yao Y Han Cheng-Tao CT Chen Hai-Tao HT Liu Fang F Zhang Gui-Ming GM Yang Wei-Yi WY Xu Jian-Feng JF Ye Ding-Wei DW

Oncotarget 20150901 26

<h4>Background</h4>We investigated whether age influences the predictiveness of genetic risk score (GRS) for prostate cancer (PCa) in a Chinese hospital-based biopsy cohort.<h4>Methods</h4>We included consecutive patients who underwent prostate biopsies in two tertiary centers between 2012 and 2014. GRS was calculated using 24 PCa-associated genetic variants and its predictiveness was assessed by area under curve (AUC).<h4>Results</h4>Of 1120 men tested, 724 with prostate-specific antigen (PSA) ...[more]

PMID: 26011940

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Project description:Importance:Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives:To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants:A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions:A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (<0.50), average (0.50-1.49), and high (≥1.50). Main Outcomes and Measures:Prostate cancer diagnosis-free survival among men of different risk groups. Results:Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P < .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P < .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to >80 years) for men at average genetic risk, and more than 80 years (95% CI, >80 to >80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance:This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies.

Project description:Objectives• To develop a '2010 Partin Nomogram' with total prostate-specific antigen (tPSA) as a continuous biomarker, in light of the fact that the current 2007 Partin Tables restrict the application of tPSA as a non-continuous biomarker by creating 'groups' for risk stratification with tPSA levels (ng/mL) of 0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0 and >10.0. • To use a 'predictiveness curve' to calculate the percentile risk of a patient among the cohort.Patients and methods• In all, 5730 and 1646 patients were treated with radical prostatectomy (without neoadjuvant therapy) between 2000 and 2005 at the Johns Hopkins Hospital (JHH) and University Clinic Hamburg-Eppendorf (UCHE), respectively. • Multinomial logistic regression analysis was performed to create a model for predicting the risk of the four non-ordered pathological stages, i.e. organ-confined disease (OC), extraprostatic extension (EPE), and seminal vesicle (SV+) and lymph node (LN+) involvement. • Patient-specific risk was modelled as a function of the B-spline basis of tPSA (with knots at the first, second and third quartiles), clinical stage (T1c, T2a, and T2b/T2c) and biopsy Gleason score (5-6, 3 + 4 = 7, 4 + 3 = 7, 8-10).Results• The '2010 Partin Nomogram' calculates patient-specific absolute risk for all four pathological outcomes (OC, EPE, SV+, LN+) given a patient's preoperative clinical stage, tPSA and biopsy Gleason score. • While having similar performance in terms of calibration and discriminatory power, this new model provides a more accurate prediction of patients' pathological stage than the 2007 Partin Tables model. • The use of 'predictiveness curves' has also made it possible to obtain the percentile risk of a patient among the cohort and to gauge the impact of risk thresholds for making decisions regarding radical prostatectomy.Conclusion• The '2010 Partin Nomogram' using tPSA as a continuous biomarker together with the corresponding 'predictiveness curve' will help clinicians and patients to make improved treatment decisions.

Dataset Information

Influence of age on predictiveness of genetic risk score for prostate cancer in a Chinese hospital-based biopsy cohort.

Publications

Influence of age on predictiveness of genetic risk score for prostate cancer in a Chinese hospital-based biopsy cohort.

Similar Datasets

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