Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci
Year: 2016
Type: article
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddw164
Authors: 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 Kasuga, Dong-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
Institutions: Vanderbilt University, Vanderbilt-Ingram Cancer Center, Seoul National University, RIKEN Center for Integrative Medical Sciences, Chonnam National University, Chonnam National University Hwasun Hospital, Shanghai Municipal Center For Disease Control Prevention, Aichi Cancer Center, Aichi Cancer Center Research Institute, Nagoya University, National Cancer Centre Japan, China Medical University, Institute of Biomedical Sciences, Academia Sinica, Taiwan Biobank, Academia Sinica, National Cancer Center, Vanderbilt University Medical Center, Shanghai Cancer Institute, Nagano Matsushiro General Hospital, Institute of Medical Science, The University of Tokyo, The University of Tokyo, Aichi Cancer Center Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Japan Agency for Medical Research and Development, National Research Foundation, Ministry of Education, Culture, Sports, Science and Technology, National Research Foundation of Korea, Ministry of Education, Science and Technology, National Institutes of Health, National Cancer Institute
Awards: Soyfood, Gene Polymorphisms and Endometrial Cancer Risk, Shanghai Breast Cancer Study, Role of Shh in developmental patterning and proliferation of digit skeleton, G232248983, G2469231085, Discovery, Biology and Risk of Inherited Variants in Breast Cancer, Cell Cycle/Apoptosis Gene Variants and Breast Cancer Risk, Cancer Risk Reduction and Diet: A Cohort Study of Women, Consortium Study to Identify Breast Cancer Susceptibility Loci, G3269002440, G3672464712, G3785286892, Genetic Factors for Breast Cancer- A genome Wide Study, G4014037350, G4025444071, Breast Cancer Survival: Lifestyle and Genetic Determinants, G4512404885, G4998947630, Genome-wide Copy Number Variation and Breast Cancer Risk, G6321546214, G7371674094, G7469613934, G8147032887, Shanghai Womens Health Study, G8907405925, Cancer Center Support Grant
OpenAlex ID: W2460875272