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Sci Rep. 2019 Nov 22;9(1):17332. doi: 10.1038/s41598-019-53654-9.

Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population.

Author information

1
Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan. siewkee.low@jfcr.or.jp.
2
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. siewkee.low@jfcr.or.jp.
3
Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
4
Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan.
5
Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
6
Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
7
Laboratory of Genome Technology, Human Genome Center, The University of Tokyo, Tokyo, Japan.
8
Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
9
Department of Genetic Diagnosis, The Cancer Institute of JFCR, Tokyo, Japan.
10
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
11
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
12
Division of Epidemiology, National Cancer Center, Tokyo, Japan.
13
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
14
Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
15
Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
16
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
17
Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
18
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
19
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
20
Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
21
Department of Molecular Cytogenetics, Tokyo Medical & Dental University, Tokyo, Japan.
22
Bioresource Research Center, Tokyo Medical & Dental University, Tokyo, Japan.
23
Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan.
24
Department of Molecular Genetics, Medical Research Institute, Tokyo Medical & Dental University, Tokyo, Japan.

Abstract

Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10-8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.

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