Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data.
<h4>Background</h4>Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease.<h4>Objectives</h4>We...
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2011
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oai:doaj.org-article:e5eabb200e4343a1a2ae91e654fe29f22021-11-18T07:33:41ZAssociation between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data.1932-620310.1371/journal.pone.0026527https://doaj.org/article/e5eabb200e4343a1a2ae91e654fe29f22011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22132073/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease.<h4>Objectives</h4>We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. METHODS AND DATA SOURCES: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study.<h4>Results</h4>Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p<0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7×10(-4)). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells.<h4>Conclusions</h4>Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.Jyotsna BatraFelicity LoseTracy O'MaraLouise MarquartCarson StephensKimberly AlexanderSrilakshmi SrinivasanRosalind A EelesDouglas F EastonAli Amin Al OlamaZsofia Kote-JaraiMichelle GuyKenneth MuirArtitaya LophatananonAneela A RahmanDavid E NealFreddie C HamdyJenny L DonovanSuzanne ChambersRobert A GardinerJoanne AitkenJohn YaxleyMary-Anne KeddaJudith A ClementsAmanda B SpurdlePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e26527 (2011) |
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Medicine R Science Q Jyotsna Batra Felicity Lose Tracy O'Mara Louise Marquart Carson Stephens Kimberly Alexander Srilakshmi Srinivasan Rosalind A Eeles Douglas F Easton Ali Amin Al Olama Zsofia Kote-Jarai Michelle Guy Kenneth Muir Artitaya Lophatananon Aneela A Rahman David E Neal Freddie C Hamdy Jenny L Donovan Suzanne Chambers Robert A Gardiner Joanne Aitken John Yaxley Mary-Anne Kedda Judith A Clements Amanda B Spurdle Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| description |
<h4>Background</h4>Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease.<h4>Objectives</h4>We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. METHODS AND DATA SOURCES: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study.<h4>Results</h4>Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p<0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7×10(-4)). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells.<h4>Conclusions</h4>Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes. |
| format |
article |
| author |
Jyotsna Batra Felicity Lose Tracy O'Mara Louise Marquart Carson Stephens Kimberly Alexander Srilakshmi Srinivasan Rosalind A Eeles Douglas F Easton Ali Amin Al Olama Zsofia Kote-Jarai Michelle Guy Kenneth Muir Artitaya Lophatananon Aneela A Rahman David E Neal Freddie C Hamdy Jenny L Donovan Suzanne Chambers Robert A Gardiner Joanne Aitken John Yaxley Mary-Anne Kedda Judith A Clements Amanda B Spurdle |
| author_facet |
Jyotsna Batra Felicity Lose Tracy O'Mara Louise Marquart Carson Stephens Kimberly Alexander Srilakshmi Srinivasan Rosalind A Eeles Douglas F Easton Ali Amin Al Olama Zsofia Kote-Jarai Michelle Guy Kenneth Muir Artitaya Lophatananon Aneela A Rahman David E Neal Freddie C Hamdy Jenny L Donovan Suzanne Chambers Robert A Gardiner Joanne Aitken John Yaxley Mary-Anne Kedda Judith A Clements Amanda B Spurdle |
| author_sort |
Jyotsna Batra |
| title |
Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| title_short |
Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| title_full |
Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| title_fullStr |
Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| title_full_unstemmed |
Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. |
| title_sort |
association between prostinogen (klk15) genetic variants and prostate cancer risk and aggressiveness in australia and a meta-analysis of gwas data. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/e5eabb200e4343a1a2ae91e654fe29f2 |
| work_keys_str_mv |
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