Molecular Cancer Epidemiology Group, Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, Queensland, Australia.
PLoS One. 2012;7(9):e44520. doi: 10.1371/journal.pone.0044520. Epub 2012 Sep 6.
The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (± 10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥ 7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the P(trend)<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r(2) ≥ 0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.
激肽释放酶相关肽酶 4（KLK4）在许多研究中被证明在前列腺肿瘤中显著过表达，被认为是前列腺癌的潜在生物标志物。KLK4 可能通过参与上皮-间充质转化、更具侵袭性的表型以及转移到骨骼中，在前列腺癌的进展中发挥作用。众所周知，遗传变异有可能影响基因表达和/或各种蛋白质特征，因此我们试图研究 KLK4 基因中的单核苷酸多态性（SNP）在前列腺癌中的可能作用。在大约 1300 例前列腺癌病例和 1300 例男性对照中，评估 KLK4 基因座（± 10 kb）中的 61 个 SNP 与前列腺癌风险和/或前列腺肿瘤侵袭性（Gleason 评分<7 与≥7）的相关性，结果发现 7 个 SNP 与前列腺癌风险呈负相关（P(trend)<0.05）。这 3 个 SNP 中的 rs268923、rs56112930 和 HapMap 标签 SNP rs7248321 位于 KLK4 上游几个 kb 处；rs1654551 编码 KLK4 长型蛋白第 22 位丝氨酸到丙氨酸的非同义取代，而其余 3 个与风险相关的 SNP，rs1701927、rs1090649 和 rs806019，位于 KLK4 下游，彼此之间高度连锁不平衡（r(2)≥0.98）。我们的研究结果提供了 KLK4 基因座遗传变异在前列腺癌易感性中的作用的提示性证据。
