Title |
Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies
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Published in |
Cancer Epidemiology, Biomarkers & Prevention, July 2014
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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
Geographical breakdown
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United Kingdom | 3 | 3% |
Japan | 1 | 1% |
Unknown | 82 | 95% |
Demographic breakdown
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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% |
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Computer Science | 10 | 12% |
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Chemistry | 2 | 2% |
Other | 16 | 19% |
Unknown | 11 | 13% |