Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population
Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population
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DOI：
10.1038/s41598-019-53654-9
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发表时间：
2019-11-22
影响因子：
4.6
通讯作者：
Miki, Yoshio
中科院分区：
文献类型：
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作者：
Low, Siew-Kee;Chin, Yoon Ming;Miki, Yoshio
全基因组关联研究已经成功地确定了大约70个与乳腺癌相关的基因组位点。由于连锁不平衡和环境暴露在不同人群中的复杂性，为了更好地预测风险，有必要进行区域全球环境影响分析。这项研究旨在调查日本人群中6,669名乳腺癌患者和21,930名女性对照的乳腺癌遗传结构并评估常见的遗传风险模型。其中9个已报道的基因座和2个新的基因座包括位于3q13.11(Alcam)的rs9862599和位于21q22.12(clic6-RUNX1)的rs75286142。来自爱知癌症中心的981例乳腺癌患者和1394名对照进行了验证性研究。对Gwas信号的通路分析表明，多巴胺受体介导的信号和蛋白质氨基酸去乙酰化与乳腺癌有关。加权遗传风险得分显示，被归入最高风险组的个人患乳腺癌的可能性大约是最低风险组的3.7倍。这项功能强大的GWAS是一项具有代表性的研究，旨在确定日本人群中与乳腺癌相关的SNPs。
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 x 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.