Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci

Mi Ryung Han, Jirong Long, Ji Yeob Choi, Siew Kee Low, Sun Seog Kweon, Ying Zheng, Qiuyin Cai, Jiajun Shi, Xingyi Guo, Keitaro Matsuo, Motoki Iwasaki, Chen Yang Shen, Mi Kyung Kim, Wanqing Wen, Bingshan Li, Atsushi Takahashi, Min Ho Shin, Yong Bing Xiang, Hidemi Ito, Yoshio KasugaDong Young Noh, Koichi Matsuda, Min Ho Park, Yu Tang Gao, Hiroji Iwata, Shoichiro Tsugane, Sue K. Park, Michiaki Kubo, Xiao Ou Shu, Daehee Kang, Wei Zheng

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Breast cancer is one of the most commonmalignancies among women worldwide. Genetic factors have been shown to play an important role in breast cancer aetiology. We conducted a two-stage genome-wide association study (GWAS) including 14 224 cases and 14 829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer. Single nucleotide polymorphisms (SNPs) in two loci were found to be associated with breast cancer risk at the genome-wide significance level. The first locus, represented by rs12118297 at 1p22.3 (near the LMO4 gene), was associated with breast cancer risk with odds ratio (OR) and (95% confidence interval (CI)) of 0.91 (0.88-0.94) and a P-value of 4.48×10-8. This association was replicated in another study, DRIVE GAME-ON Consortium, including 16 003 cases and 41 335 controls of European ancestry (OR=0.95, 95% CI=0.91-0.99, P-value=0.019). The second locus, rs16992204 at 21q22.12 (near the LINC00160 gene), was associated with breast cancer risk with OR (95% CI) of 1.13 (1.07-1.18) and a P-value of 4.63×10-8. The risk allele frequency for this SNP is zero in European-ancestry populations in 1000 Genomes Project and thus its association with breast cancer risk cannot be assessed in DRIVE GAME-ON Consortium. Functional annotation using the ENCODE data indicates that rs12118297might be located in a repressed element and locus 21q22.12 may affect breast cancer risk through regulating LINC00160 expressions and interaction with oestrogen receptor signalling. Our findings provide additional insights into the genetics of breast cancer.

Original languageEnglish
Pages (from-to)3361-3371
Number of pages11
JournalHuman molecular genetics
Issue number15
Publication statusPublished - 01-08-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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