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

作者：Elgazzar Seham; Zembutsu Hitoshi; Takahashi Atsushi; Kubo Michiaki; Aki Fuminori; Hirata Koichi; Takatsuka Yuichi; Okazaki Minoru; Ohsumi Shozo; Yamakawa Takashi; Sasa Mitsunori; Katagiri Toyomasa; Miki Yoshio; Nakamura Yusuke^*

来源：Journal of Human Genetics, 2012, 57(12): 766-771.

DOI：10.1038/jhg.2012.108

• breast cancer in the Japanese population
• FGFR2 gene
• GWAS
• hormonal receptor-positive breast cancer
• SIAH2 gene
• 3q25.1 locus
• 10q26 locus

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 %26lt;1 x 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 x 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 x 10(-8) with OR 1.22. Our results suggest a novel susceptibility locus on chromosome 3q25.1 for a HRP breast cancer. Journal of Human Genetics (2012) 57, 766-771; doi:10.1038/jhg.2012.108; published online 6 September 2012

• 出版日期2012-12
• 单位河北医科大学