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学科主题: 临床医学
题名:
Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population
作者: Ruan, Yuan1; Song, Ai-Ping1; Wang, Hui1; Xie, Yun-Tao2; Han, Ji-Yuan1; Sajdik, Constantin3; Tian, Xin-Xia1; Fang, Wei-Gang1
关键词: Aurora-A ; AURKA ; BRCA1 ; breast cancer ; SNP ; risk
刊名: JOURNAL OF PATHOLOGY
发表日期: 2011-12-01
DOI: 10.1002/path.2902
卷: 225, 期:4, 页:535-543
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Pathology
研究领域[WOS]: Oncology ; Pathology
关键词[WOS]: AURORA-A ; CENTROSOME AMPLIFICATION ; COMMON VARIANTS ; HUMAN GENOME ; RISK ; HAPLOTYPE ; IDENTIFICATION
英文摘要:

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

语种: 英语
所属项目编号: 30670805 ; 30770829 ; 108003 ; 2007AA02Z477
项目资助者: Beijing Municipal Education Commission ; National Natural Science Foundation of China ; Chinese Ministry of Education ; National High Technology Research and Development Programme of China
WOS记录号: WOS:000297299500007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62805
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Key Lab Carcinogenesis & Translat Res, Dept Pathol,Minist Educ,Sino Austrian Ctr Biomark, Beijing 100191, Peoples R China
2.Peking Univ, Sch Oncol, Beijing Canc Hosp & Inst, Breast Ctr, Beijing 100142, Peoples R China
3.Leopold Franzens Univ, Inst Analyt Chem & Radiochem, A-6020 Innsbruck, Austria

Recommended Citation:
Ruan, Yuan,Song, Ai-Ping,Wang, Hui,et al. Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population[J]. JOURNAL OF PATHOLOGY,2011,225(4):535-543.
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