12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population
12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population
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DOI：
10.1038/s41467-019-12267-6
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发表时间：
2019-09-27
影响因子：
16.6
通讯作者：
Nakagawa, Hidewaki
中科院分区：
文献类型：
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作者：
Takata, Ryo;Takahashi, Atsushi;Nakagawa, Hidewaki
全基因组关联研究（GWAS）已经确定了170个与前列腺癌（PCa）风险相关的基因位点，但其中大多数是在欧洲人群中发现的。我们在这里进行了一项GWAS和复制研究，使用了一个大型日本队列（9,906例和83,943例男性对照）来确定与PCa风险相关的新的易感位点。我们发现了12个新的PCa位点，包括rs1125927 （TMEM17, P = 3.95 × 10(-16)）、rs73862213 （GATA2, P = 5.87 × 10(-23)）、rs77911174 （ZMIZ1, P = 5.28 × 10(-20)）和rs138708 (SUN2, P = 1.13 × 10(-15))，其中7个位点在欧洲人群中具有极低的次要等位基因频率。此外，我们利用本研究中与日本PCa风险显著相关的82个snp对日本PCa患者的多基因风险进行了分层，发现早发病例和有PCa家族史的病例在遗传高危人群中富集。我们的研究为前列腺癌的遗传机制提供了重要的见解，并促进了日本人群中前列腺癌的风险分层。
Genome-wide association studies (GWAS) have identified similar to 170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 x 10(-16)), rs73862213 (GATA2, P = 5.87 x 10(-23)), rs77911174 (ZMIZ1, P = 5.28 x 10(-20)), and rs138708 (SUN2, P = 1.13 x 10(-15)), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.