Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness

Lose, Felicity, Batra, Jyotsna, O'Mara, Tracy, Fahey, Paul, Marquart, Louise, Eeeles, Ros A., Easton, Douglas F., Olama, Ali Amin Al, Kote-Jarai, Zsofia, Guy, Michelle, Muir, Kenneth, Lophatananon, Artitaya, Rahman, Aneela A., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Chambers, Suzanne, Gardiner, Robert A., Aitken, Joanne F., Yaxley, John, Alexander, Kimberly, Clements, Judith A., Spurdle, Amanda B., Kedda, Mary-Anne and Australian Prostate Cancer BioResearch (2011) Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness. Urologic Oncology: Seminars and Original Investigations Urologic Oncology: Seminars and Original Investigations, : .

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Author Lose, Felicity
Batra, Jyotsna
O'Mara, Tracy
Fahey, Paul
Marquart, Louise
Eeeles, Ros A.
Easton, Douglas F.
Olama, Ali Amin Al
Kote-Jarai, Zsofia
Guy, Michelle
Muir, Kenneth
Lophatananon, Artitaya
Rahman, Aneela A.
Neal, David E.
Hamdy, Freddie C.
Donovan, Jenny L.
Chambers, Suzanne
Gardiner, Robert A.
Aitken, Joanne F.
Yaxley, John
Alexander, Kimberly
Clements, Judith A.
Spurdle, Amanda B.
Kedda, Mary-Anne
Australian Prostate Cancer BioResearch
Title Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness
Formatted title Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness
Journal name Urologic Oncology: Seminars and Original Investigations Urologic Oncology: Seminars and Original Investigations  (ERA 2012 Listed)    (ERA 2010 Rank C)   Check publisher's open access policy
Publication date 2011-07-08
Sub-type Article
DOI 10.1016/j.urolonc.2011.05.011
ISSN 1078-1439
1873-2496
1081-0943
Total pages 9
Place of publication Philadelphia, PA, U.S.A.
Publisher Elsevier
Collection year 2012
Language eng
Formatted abstract The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis. We sought to elucidate the role of common genetic variation in four of the Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor aggressiveness.

Genotyping of all 22 tagging single nucleotide polymorphisms (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in approximately 1,000 prostate cancer cases and 1,300 male controls from Australia. Data from any positive results were also accessed for 1,844 cases and 1,886 controls from a previously published prostate cancer genome-wide association study set from the United Kingdom.

For one SNP in KLK12, rs3865443, there was evidence for association with prostate cancer risk of similar direction and magnitude in the replication set to that seen in the Australian cohort. We conducted genotyping of a further 309 prostate cancer cases, and combined analyses revealed an increased risk of prostate cancer for carriers of the rare homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04–1.57; P = 0.018). No other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated with prostate cancer risk or tumor aggressiveness.

Analysis of a combined sample of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be marginally statistically significantly associated with risk of prostate cancer. Considering the total number of SNPs investigated in this study, this finding should be interpreted cautiously and requires additional validation from very large datasets such as those of the Prostate Cancer Association group to investigate cancer associated alterations (PRACTICAL) Consortium.
Keyword Prostate cancer
Kallikreins
Single nucleotide polymorphism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes In press - Available online 8 July 2011.

 
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Created: Wed, 24 Aug 2011, 15:02:14 EST by Vicki Percival on behalf of UQ Centre for Clinical Research