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Hum Mol Genet. 2016 Aug 1;25(15):3361-3371. doi: 10.1093/hmg/ddw164. Epub 2016 Jun 27.

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

Author information

1
Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
2
Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA jirong.long@vanderbilt.edu.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
4
Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea.
5
Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Yokohama 351-0198, Japan.
6
Department of Preventive Medicine, Chonnam National University Medical School, Gwangju 61469, South Korea.
7
Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun 58128, South Korea.
8
Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
9
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
10
Department of Epidemiology, Nagoya University Graduates School of Medicine, Nagoya 464-8681, Japan.
11
Epidemiology Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
12
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
13
Taiwan Biobank, Academia Sinica, Taipei 115, Taiwan.
14
College of Public Health, China Medical University, Taichung 404, Taiwan.
15
Division of Cancer Epidemiology and Management, National Cancer Center, Gyeonggi-do 10408, South Korea.
16
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
17
Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, China.
18
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
19
Department of Surgery, Nagano Matsushiro General Hospital, Nagano 381-1231, Japan.
20
Department of Surgery, Seoul National University College of Medicine, Seoul 03080, South Korea.
21
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan.
22
Department of Surgery, Chonnam National University Medical School, Gwangju 61469, South Korea.
23
Department of Breast Oncology, Aichi Cancer Center Central Hospital, Nagoya 464-8681, Japan.
24
Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
25
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea.
26
Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama 351-0198, Japan.

Abstract

Breast cancer is one of the most common malignancies 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 rs12118297 might 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.

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