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- Hoffmann, Thomas J., et al.
(author)
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Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa - such as genetics - can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.
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- Cremers, Ruben G., et al.
(author)
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The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers
- 2015
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In: Urologic Oncology: Seminars and Original Investigations. - : Elsevier BV. - 1078-1439. ; 33:5, s. 19-202
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. Materials and methods: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level≥3.0. ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate biopsies and (2) as an indicator for prostate biopsies among men with an elevated PSA level. PC detected up to the 2-year screening was used as gold standard as end-of-study biopsies were not performed. Results: Overall, 23 PCs were diagnosed, 20 of which were in men who had an elevated PSA level in the initial screening round. (1) PCA3, successfully determined in 552 participants, was elevated in 188 (cutoff≥25; 34%) or 134 (cutoff≥35; 24%) participants, including 2 of the 3 PCs missed by PSA. PCA3 would have added 157 (≥25; 28%) or 109 (≥35; 20%) biopsy sessions to screening with PSA only. (2) Elevated PCA3 as a requirement for biopsies in addition to PSA would have saved 37 (cutoff≥25) or 43 (cutoff≥35) of the 68 biopsy sessions, and 7 or 11 PCs would have been missed, respectively, including multiple high-risk PCs. So far, PCA3 performed best among BRCA2 mutation carriers, but the numbers are still small. Because PCA3 was not used to indicate prostate biopsies, its true diagnostic value cannot be calculated. Conclusions: The results do not provide evidence for PCA3 as a useful additional indicator of prostate biopsies in BRCA mutation carriers, as many participants had an elevated PCA3 in the absence of PC. This must be interpreted with caution because PCA3 was not used to indicate biopsies. Many participants diagnosed with PC had low PCA3, making it invalid as a restrictive marker for prostate biopsies in men with elevated PSA levels.
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- Kalter, J., et al.
(author)
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Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer : An individual patient data meta-analysis of 22 RCTs
- 2018
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In: Psycho-Oncology. - : WILEY. - 1057-9249 .- 1099-1611. ; 27:4, s. 1150-1161
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Research review (peer-reviewed)abstract
- Objective: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. Methods: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (=0.14,95%CI=0.06;0.21), EF ( beta = 0.13,95%CI = 0.05;0.20), and SF (beta = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.
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- Petersen, M. A., et al.
(author)
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The EORTC CAT Core-The computer adaptive version of the EORTC QLQ-C30 questionnaire
- 2018
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 100, s. 8-16
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Journal article (peer-reviewed)abstract
- Background: To optimise measurement precision, relevance to patients and flexibility, patient-reported outcome measures (PROMs) should ideally be adapted to the individual patient/study while retaining direct comparability of scores across patients/studies. This is achievable using item banks and computerised adaptive tests (CATs). The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) is one of the most widely used PROMs in cancer research and clinical practice. Here we provide an overview of the research program to develop CAT versions of the QLQ-C30's 14 functional and symptom domains. Methods: The EORTC Quality of Life Group's strategy for developing CAT item banks consists of: literature search to identify potential candidate items; formulation of new items compatible with the QLQ-C30 item style; expert evaluations and patient interviews; field-testing and psychometric analyses, including factor analysis, item response theory calibration and simulation of measurement properties. In addition, software for setting up, running and scoring CAT has been developed. Results: Across eight rounds of data collections, 9782 patients were recruited from 12 countries for the field-testing. The four phases of development resulted in a total of 260 unique items across the 14 domains. Each item bank consists of 7-34 items. Psychometric evaluations indicated higher measurement precision and increased statistical power of the CAT measures compared to the QLQ-C30 scales. Using CAT, sample size requirements may be reduced by approximately 20-35% on average without loss of power. Conclusions: The EORTC CAT Core represents a more precise, powerful and flexible measurement system than the QLQ-C30. It is currently being validated in a large independent, international sample of cancer patients. (C) 2018 Elsevier Ltd. All rights reserved.
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