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学科主题: 基础医学
题名:
Association of Germline Variation in CCNE1 and CDK2 with Breast Cancer Risk, Progression and Survival among Chinese Han Women
作者: Han, Ji-Yuan1; Wang, Hui1; Xie, Yun-Tao2; Li, Yan1; Zheng, Li-Yuan1; Ruan, Yuan1; Song, Ai-Ping1; Tian, Xin-Xia1; Fang, Wei-Gang1
刊名: PLOS ONE
发表日期: 2012-11-21
DOI: 10.1371/journal.pone.0049296
卷: 7, 期:11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: SINGLE-NUCLEOTIDE POLYMORPHISMS ; CYCLE CONTROL GENES ; OVARIAN-CANCER ; LINKAGE DISEQUILIBRIUM ; BLADDER-CANCER ; HUMAN GENOME ; LUNG-CANCER ; SUSCEPTIBILITY ; POPULATION ; VARIANTS
英文摘要:

Background: Somatic alterations of cyclin-dependent kinase 2 (CDK2)-cyclin E complex have been shown to contribute to breast cancer (BC) development and progression. This study aimed to explore the effects of single nucleotide polymorphisms (SNPs) in CDK2 and CCNE1 (a gene encoding G1/S specific cyclin E1 protein, formerly called cyclin E) on BC risk, progression and survival in a Chinese Han population.

Methodology/Principal Findings: We herein genotyped 6 haplotype-tagging SNPs (htSNPs) of CCNE1 and 2 htSNPs of CDK2 in 1207 BC cases and 1207 age-matched controls among Chinese Han women, and then reconstructed haplotype blocks according to our genotyping data and linkage disequilibrium status of these htSNPs. For CCNE1, the minor allele homozygotes of three htSNPs were associated with BC risk (rs3218035: adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI] = 1.69-6.67; rs3218038: aOR = 1.81, 95% CI = 1.22-2.70; rs3218042: aOR = 2.64, 95% CI = 1.31-5.34), and these three loci showed a dose-dependent manner in increasing BC risk (P-trend = 0.0001). Moreover, the 5-SNP haplotype CCGTC, which carried none of minor alleles of the 3 at-risk SNPs, was associated with a favorable event-free survival (hazard ratio [HR] = 0.53, 95% CI = 0.32-0.90). Stratified analysis suggested that the minor-allele homozygote carriers of rs3218038 had a worse event-free survival among patients with aggressive tumours (in tumour size >2 cm group: HR = 2.06, 95% CI = 1.06-3.99; in positive lymph node metastasis group: HR = 2.41, 95% CI = 1.15-5.03; in stage II-IV group: HR = 2.03, 95% CI = 1.09-3.79). For CDK2, no significant association was found.

Conclusions/Significance: This study indicates that genetic variants in CCNE1 may contribute to BC risk and survival in Chinese Han population. They may become molecular markers for individual evaluation of BC susceptibility and prognosis. Nevertheless, further validation studies are needed.

语种: 英语
所属项目编号: 81171961 ; 30670805 ; 108003
项目资助者: National Natural Science Foundation of China ; Chinese Ministry of Education ; Beijing Municipal Education Commission
WOS记录号: WOS:000311821000038
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66779
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Dept Pathol, Key Lab Carcinogenesis & Translat Res, Sch Basic Med Sci,Minist Educ,Hlth Sci Ctr, Beijing 100871, Peoples R China
2.Peking Univ, Breast Ctr, Sch Oncol, Beijing Canc Hosp & Inst, Beijing 100871, Peoples R China

Recommended Citation:
Han, Ji-Yuan,Wang, Hui,Xie, Yun-Tao,et al. Association of Germline Variation in CCNE1 and CDK2 with Breast Cancer Risk, Progression and Survival among Chinese Han Women[J]. PLOS ONE,2012,7(11).
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