Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies

Knipe, Duleeka W., Evans, David M., Kemp, John P., Eeles, Rosalind, Easton, Douglas F., Kote-Jarai, Zsofia, Al Omama, Ali Amin, Benlloch, Sara, Donovan, Jenny L., Hamdy, Freddie C., Neal, David E., Davey Smith, George, Lathrop, Mark and Martin, Richard M. (2014) Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies. Cancer Epidemiology, Biomarkers and Prevention, 23 7: 1356-1365. doi:10.1158/1055-9965.EPI-13-0889

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Author Knipe, Duleeka W.
Evans, David M.
Kemp, John P.
Eeles, Rosalind
Easton, Douglas F.
Kote-Jarai, Zsofia
Al Omama, Ali Amin
Benlloch, Sara
Donovan, Jenny L.
Hamdy, Freddie C.
Neal, David E.
Davey Smith, George
Lathrop, Mark
Martin, Richard M.
Title Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies
Journal name Cancer Epidemiology, Biomarkers and Prevention   Check publisher's open access policy
ISSN 1055-9965
1538-7755
Publication date 2014-07-01
Sub-type Article (original research)
DOI 10.1158/1055-9965.EPI-13-0889
Open Access Status File (Author Post-print)
Volume 23
Issue 7
Start page 1356
End page 1365
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
Background: Only a minority of the genetic components of prostate cancer risk have been explained. Some observed associations of SNPs with prostate cancer 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 prostate cancer (ProtecT: 1,146 cases and 1,804 controls); meta-analyzed the results with those from the previously published UK Genetic Prostate Cancer Study (1,854 cases and 1,437 controls); investigated associations of SNPs with prostate cancer using either “low” (PSA < 0.5 ng/mL) or “high” (PSA ≥ 3 ng/mL, biopsy negative) PSA controls; and investigated associations of SNPs with PSA.

Results: The ProtecT GWAS confirmed previously reported associations of prostate cancer at three loci: 10q11.23, 17q24.3, and 19q13.33. The meta-analysis confirmed associations of prostate cancer with SNPs near four previously identified loci (8q24.21,10q11.23, 17q24.3, and 19q13.33). When comparing prostate cancer cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849, and rs2735839 were associated with an increased risk of prostate cancer, but the effect-estimates were attenuated to the null when using high PSA controls (Pheterogeneity in effect-estimates < 0.04). We found a novel inverse association of rs9311171-T with circulating PSA.

Conclusions: Differences in effect-estimates for prostate cancer observed when comparing low versus 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 prostate cancer risk to carefully consider the influence of control selection criteria.
Keyword Prostate specific antigen
Research design
Prostate cancer
Case-control studies
Genome wide association studies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Also known as "Genetic variation in protein specific antigen detected prostate cancer and the effect of control selection on genetic association studies".

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
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Created: Wed, 11 Jun 2014, 21:52:25 EST by Kylie Hengst on behalf of UQ Diamantina Institute