Publication year
2010Author(s)
Source
Science Translational Medicine, 2, 62, (2010), pp. 62ra92ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Health Evidence
Urology
Laboratory of Genetic, Endocrine and Metabolic Diseases
Former Organization
Epidemiology, Biostatistics & HTA
Journal title
Science Translational Medicine
Volume
vol. 2
Issue
iss. 62
Page start
p. 62ra92
Page end
p. 62ra92
Subject
IGMD 6: Hormonal regulation; NCEBP 1: Molecular epidemiology; NCEBP 2: Evaluation of complex medical interventions; ONCOL 5: Aetiology, screening and detectionAbstract
Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 x 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.
This item appears in the following Collection(s)
- Academic publications [238430]
- Faculty of Medical Sciences [90359]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.