12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population

Nat Commun. 2019 Sep 27;10(1):4422. doi: 10.1038/s41467-019-12267-6.

Abstract

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 × 10-16), rs73862213 (GATA2, P = 5.87 × 10-23), rs77911174 (ZMIZ1, P = 5.28 × 10-20), and rs138708 (SUN2, P = 1.13 × 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • GATA2 Transcription Factor / genetics
  • Gene Frequency
  • Genetic Loci / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study*
  • Genotype
  • Genotyping Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Japan
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / genetics*
  • Risk Factors
  • Transcription Factors / genetics
  • Transcriptome

Substances

  • GATA2 Transcription Factor
  • GATA2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SUN2 protein, human
  • TMEM170A protein, human
  • Transcription Factors
  • ZMIZ1 protein, human