Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in the Chinese population.
Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in the Chinese population.
复制标题
中国人群中 C2orf43、FOXP4、GPRC6A 和 RFX6 基因与前列腺癌关联的复制和精细定位
DOI：
10.1371/journal.pone.0037866
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu XG
中科院分区：
文献类型：
--
作者：
Long QZ;Du YF;Ding XY;Li X;Song WB;Yang Y;Zhang P;Zhou JP;Liu XG
前列腺癌是全世界男性死亡的主要原因。最近的一项全基因组关联研究（GWAS）在日本人群中发现了5个新的前列腺癌易感基因座。本研究旨在复制和精细定位这五个基因座与中国汉族人群前列腺癌的潜在关联。在第一阶段的研究中，我们测试了五个单核苷酸多态性（SNP），这些SNP在日本人的原始GWAS中显示出最强的关联证据。研究样本包括1，169名中国汉族人，其中483名患者和686名健康对照。然后在第二阶段，对第一阶段成功复制的SNP的侧翼SNP进行基因分型，并测试其与前列腺癌的关联，以精细定位那些显著的关联信号。我们成功复制了rs13385191（位于C2orf43基因，P = 8.60 × 10 − 5）、rs12653946（P = 1.33 × 10 − 6）、rs1983891（FOXP4，P = 6.22 × 10 − 5）和rs339331（GPRC6A/RFX6，P = 1.42 × 10 − 5）与前列腺癌的关联。 rs12653946的最显著比值比（OR）记录为1.41（95%置信区间1.18 - 1.68）。在本研究中，Rs9600079与前列腺癌无显著相关性（P = 8.07 × 10 − 2）。 第二阶段的研究完善了这些关联信号，并确定了几个SNP与前列腺癌的关联比第一阶段测试的SNP更显著。我们的研究结果进一步支持C2orf43，FOXP4，GPRC6A和RFX6基因与东亚人群前列腺癌的关联。本研究还对原始GWAS中报告的新位点进行了更详细的描述。仍需要进一步的工作来确定功能变异并最终阐明潜在的生物学机制。
Prostate cancer represents the leading cause of male death across the world. A recent genome-wide association study (GWAS) identified five novel susceptibility loci for prostate cancer in the Japanese population. This study is to replicate and fine map the potential association of these five loci with prostate cancer in the Chinese Han population. In Phase I of the study, we tested the five single nucleotide polymorphisms (SNPs) which showed the strongest association evidence in the original GWAS in Japanese. The study sample consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls. Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I were genotyped and tested for association with prostate cancer to fine map those significant association signals. We successfully replicated the association of rs13385191 (located in the C2orf43 gene, P = 8.60×10−5), rs12653946 (P = 1.33×10−6), rs1983891 (FOXP4, P = 6.22×10−5), and rs339331 (GPRC6A/RFX6, P = 1.42×10−5) with prostate cancer. The most significant odds ratio (OR) was recorded as 1.41 (95% confidence interval 1.18–1.68) for rs12653946. Rs9600079 did not show significant association (P = 8.07×10−2) with prostate cancer in this study. The Phase II study refined these association signals, and identified several SNPs showing more significant association with prostate cancer than the very SNPs tested in Phase I. Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations. This study also characterized the novel loci reported in the original GWAS with more details. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.
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