Evaluation of Multiple Risk-Associated Single Nucleotide Polymorphisms Versus Prostate-Specific Antigen at Baseline to Predict Prostate Cancer in Unscreened Men
Författare
Summary, in English
Background: Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear. Objective: Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men. Design, setting, and participants: This study used a nested case-control design based on the Malmo Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005. Measurements: We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer. Results and limitations: Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p < 0.001). Seven SNPs at five independent loci were associated with advanced prostate cancer defined as clinical stage >= T3 or evidence of metastasis at diagnosis. Four independent SNPs were associated with advanced or aggressive cancer defined as stage >= T3, metastasis, Gleason score >= 8, or World Health Organization grade 3 at diagnosis. Prostate cancer risk prediction with SNPs alone was less accurate than with PSA at baseline (area under the curve of 0.57 vs 0.79), with no benefit from combining SNPs with PSA. This study is limited by our reliance on clinical diagnosis of prostate cancer; there are likely undiagnosed cases among our control group. Conclusions: Only a few previously reported SNPs were associated with prostate cancer risk in the large prospective Diet and Cancer cohort in Malmo, Sweden. SNPs were less useful in predicting prostate cancer risk than PSA at baseline. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Avdelning/ar
- Klinisk kemi, Malmö
- Genomik, diabetes och endokrinologi
- Urologisk cancerforskning, Malmö
- Kirurgi
- Institutionen för kliniska vetenskaper, Malmö
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2012
Språk
Engelska
Sidor
471-477
Publikation/Tidskrift/Serie
European Urology
Volym
61
Issue
3
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Urology and Nephrology
Nyckelord
- Prostate cancer
- Biomarkers
- SNPs
- PSA
- Sensitivity and specificity
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
- Genomics, Diabetes and Endocrinology
- Urological cancer, Malmö
- Surgery
ISBN/ISSN/Övrigt
- ISSN: 1873-7560