A genome-wide association study identifies a genetic variant in the SIAH2 locus associated with hormonal receptor-positive breast cancer in Japanese

J Hum Genet. 2012 Dec;57(12):766-71. doi: 10.1038/jhg.2012.108. Epub 2012 Sep 6.


In Japan, breast cancer is the most common cancer among women and the second leading cause of cancer death among women worldwide. To identify genetic variants associated with the disease susceptibility, we performed a genome-wide association study (GWAS) using a total of 1086 Japanese female patients with hormonal receptor-positive (HRP) breast cancer and 1816 female controls. We selected 33 single-nucleotide polymorphisms (SNPs) with suggestive associations in GWAS (P-value of <1 × 10(-4)) as well as 4 SNPs that were previously implicated their association with breast cancer for further replication by an independent set of 1653 cases and 2797 controls. We identified significant association of the disease with a SNP rs6788895 (P(combined) of 9.43 × 10(-8) with odds ratio (OR) of 1.22) in the SIAH2 (intron of seven in absentia homolog 2) gene on chromosome 3q25.1 where the involvement in estrogen-dependent diseases was suggested. In addition, rs3750817 in intron 2 of the fibroblast growth factor receptor 2 gene, which was reported to be associated with breast cancer susceptibility, was significantly replicated with P(combined) of 8.47 × 10(-8) with OR=1.22. Our results suggest a novel susceptibility locus on chromosome 3q25.1 for a HRP breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Case-Control Studies
  • Chromosomes, Human, Pair 3 / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Neoplasms, Hormone-Dependent / genetics*
  • Neoplasms, Hormone-Dependent / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Polymorphism, Single Nucleotide / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics
  • Receptors, Estrogen / metabolism*
  • Risk Factors
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism


  • Nuclear Proteins
  • Receptors, Estrogen
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2