Department of Urology, Iwate Medical University, Morioka, 020-8505, Japan.
Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.
Genome-wide association studies (GWAS) have identified ~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 × 10), rs73862213 (GATA2, P = 5.87 × 10), rs77911174 (ZMIZ1, P = 5.28 × 10), and rs138708 (SUN2, P = 1.13 × 10), 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.
全基因组关联研究(GWAS)已经确定了约 170 个与前列腺癌(PCa)风险相关的遗传位点,但其中大多数是在欧洲人群中发现的。我们在这里使用一个大型的日本队列(9906 例病例和 83943 名男性对照)进行 GWAS 和复制研究,以确定与 PCa 风险相关的新的易感位点。我们发现了 12 个与 PCa 相关的新位点,包括 rs1125927(TMEM17,P=3.95×10)、rs73862213(GATA2,P=5.87×10)、rs77911174(ZMIZ1,P=5.28×10)和 rs138708(SUN2,P=1.13×10),其中 7 个在欧洲人群中的次要等位基因频率极低。此外,我们使用与我们的研究中与日本 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分层,发现早发性病例和有 PCa 家族史的病例在遗传高风险人群中更为富集。我们的研究为 PCa 的遗传机制提供了重要的见解,并有助于日本人群中 PCa 的风险分层。