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Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies

Overview of attention for article published in Cancer Epidemiology, Biomarkers & Prevention, July 2014
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Title
Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies
Published in
Cancer Epidemiology, Biomarkers & Prevention, July 2014
DOI 10.1158/1055-9965.epi-13-0889
Pubmed ID
Authors

Duleeka W. Knipe, David M. Evans, John P. Kemp, Rosalind Eeles, Douglas F. Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Jenny L. Donovan, Freddie C. Hamdy, David E. Neal, George Davey Smith, Mark Lathrop, Richard M. Martin

Abstract

Background: Only a minority of the genetic component of prostate cancer (PrCa) risk has been explained. Some observed associations of single nucleotide polymorphisms (SNPs) with PrCa might arise from associations of these SNPs with circulating prostate specific antigen (PSA) because PSA values are used to select controls. Methods: We undertook a genome-wide association study (GWAS) of screen detected PrCa (ProtecT 1146 cases and 1804 controls); meta-analysed the results with those from the previously published UK Genetic Prostate Cancer Study (1854 cases and 1437 controls); investigated associations of SNPs with PrCa using either 'low' (PSA ≤0.5ng/ml) or 'high' (PSA ≥3ng/ml, biopsy negative) PSA controls; and investigated associations of SNPs with PSA. Results: The ProtecT GWAS confirmed previously reported associations of PrCa at 3 loci: 10q11.23, 17q24.3 and 19q13.33. The meta-analysis confirmed associations of PrCa with SNPs near 4 previously identified loci (8q24.21,10q11.23, 17q24.3 and 19q13.33). When comparing PrCa cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849 and rs2735839 were associated with an increased risk of PrCa, but the effect-estimates were attenuated to the null when using high PSA controls (p for heterogeneity in effect-estimates<0.04). We found a novel inverse association of rs9311171-T with circulating PSA. Conclusions: Differences in effect estimates for PrCa observed when comparing low vs. high PSA controls, may be explained by associations of these SNPs with PSA. Impact: These findings highlight the need for inferences from genetic studies of PrCa risk to carefully consider the influence of control selection criteria.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 86 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 3%
Japan 1 1%
Unknown 82 95%

Demographic breakdown

Readers by professional status Count As %
Other 16 19%
Student > Bachelor 14 16%
Professor 13 15%
Researcher 10 12%
Student > Ph. D. Student 8 9%
Other 16 19%
Unknown 9 10%
Readers by discipline Count As %
Medicine and Dentistry 25 29%
Agricultural and Biological Sciences 16 19%
Computer Science 10 12%
Biochemistry, Genetics and Molecular Biology 6 7%
Chemistry 2 2%
Other 16 19%
Unknown 11 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 May 2014.
All research outputs
#20,688,303
of 25,411,814 outputs
Outputs from Cancer Epidemiology, Biomarkers & Prevention
#3,856
of 4,852 outputs
Outputs of similar age
#177,701
of 242,270 outputs
Outputs of similar age from Cancer Epidemiology, Biomarkers & Prevention
#50
of 63 outputs
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