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

    Author
    Lose, Felicity
    Batra, Jyotsna
    O'Mara, Tracy
    Fahey, Paul
    Marquart, Louise
    A. Eeles, Ros
    F. Easton, Douglas
    Al Olama, Ali Amin
    Kote-Jarai, Zsofia
    Guy, Michelle
    Muir, Kenneth
    Lophatananon, Artitaya
    A. Rahman, Aneela
    E. Neal, David
    C. Hamdy, Freddie
    L. Donovan, Jenny
    Chambers, Suzanne
    A. Gardiner, Robert
    Aitken, Joanne
    Yaxley, John
    Alexander, Kimberley
    A. Clements, Judith
    B. Spurdle, Amanda
    Kedda, Mary-Anne
    Prostate Cancer BioResource, The Australian
    Year published
    2011
    Metadata
    Show full item record
    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 ...
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    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.
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    Journal Title
    Urologic Oncology: Seminars and Original Investigations
    Volume
    31
    Issue
    5
    DOI
    https://doi.org/10.1016/j.urolonc.2011.05.011
    Copyright Statement
    © 2011 Felicity et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
    Subject
    Cancer Genetics
    Publication URI
    http://hdl.handle.net/10072/41624
    Collection
    • Journal articles

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