Molecular Cancer Epidemiology group, Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Urol Oncol. 2013 Jul;31(5):635-43. doi: 10.1016/j.urolonc.2011.05.011. Epub 2011 Jul 8.
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.
人类组织激肽释放酶家族由 15 个基因组成，其中大多数在癌症中表现出差异表达，并且是癌症预后的指标。我们试图阐明四个激肽释放酶基因 KLK5、KLK6、KLK12 和 KLK13 中的常见遗传变异在前列腺癌风险和肿瘤侵袭性中的作用。在大约 1000 例前列腺癌病例和 1300 名澳大利亚男性对照中，对 KLK5、KLK6、KLK12 和 KLK13 基因中的所有 22 个标记单核苷酸多态性（tagSNP）进行了基因分型。还对来自英国之前发表的前列腺癌全基因组关联研究的 1844 例病例和 1886 例对照中任何阳性结果的数据进行了评估。在 KLK12 中的一个 SNP（rs3865443）中，在复制组中发现与澳大利亚队列中看到的相似方向和程度的前列腺癌风险相关。我们对另外 309 例前列腺癌病例进行了基因分型，并对联合分析显示，rs3865443 罕见纯合基因型携带者的前列腺癌风险增加（OR 1.28，95%CI 1.04-1.57；P=0.018）。KLK5、KLK6 和 KLK13 基因中的其他 tagSNP 与前列腺癌风险或肿瘤侵袭性均无一致相关性。对 3153 例病例和 3199 例对照的综合样本分析显示，KLK12 tagSNP rs3865443 与前列腺癌风险呈边缘统计学显著相关。考虑到本研究中调查的 SNP 总数，这一发现应谨慎解释，并需要来自前列腺癌协会（Prostate Cancer Association）等大型数据集的进一步验证，以研究与癌症相关的改变（PRACTICAL）联合会。
