Association of Germline Variation in CCNE1 and CDK2 with Breast Cancer Risk, Progression and Survival among Chinese Han Women

被引：21

作者：

Han, Ji-Yuan ^{[1
]}

Wang, Hui ^{[1
]}

Xie, Yun-Tao ^{[2
]}

Li, Yan ^{[1
]}

Zheng, Li-Yuan ^{[1
]}

Ruan, Yuan ^{[1
]}

Song, Ai-Ping ^{[1
]}

Tian, Xin-Xia ^{[1
]}

Fang, Wei-Gang ^{[1
]}

机构：

[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

来源：

PLOS ONE | 2012年 / 7卷 / 11期

基金：

中国国家自然科学基金;

关键词：

SINGLE-NUCLEOTIDE POLYMORPHISMS; CYCLE CONTROL GENES; OVARIAN-CANCER; LINKAGE DISEQUILIBRIUM; BLADDER-CANCER; HUMAN GENOME; LUNG-CANCER; SUSCEPTIBILITY; POPULATION; VARIANTS;

D O I：

10.1371/journal.pone.0049296

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：11

共 39 条

[11] Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer [J].

Gayther, Simon A. ;

Song, Honglin ;

Ramus, Susan J. ;

Kjaer, Susan Krueger ;

Whittemore, Alice S. ;

Quaye, Lydia ;

Tyrer, Jonathan ;

Shadforth, Danielle ;

Hogdall, Estrid ;

Hogdall, Claus ;

Blaeker, Jan ;

DiCioccio, Richard ;

McGuire, Valerie ;

Webb, Penelope M. ;

Beesley, Jonathan ;

Green, Adele C. ;

Whiteman, David C. ;

Goodman, Marc T. ;

Lurie, Galina ;

Carney, Michael E. ;

Modugno, Francesmary ;

Ness, Roberta B. ;

Edwards, Robert P. ;

Moysich, Kirsten B. ;

Goode, Ellen L. ;

Couch, Fergus J. ;

Cunningham, Julie M. ;

Sellers, Thomas A. ;

Wu, Anna H. ;

Pike, Malcolm C. ;

Iversen, Edivin S. ;

Marks, Jeffrey R. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Easton, Douglas F. ;

Jacobs, Ian ;

Ponder, Bruce A. J. ;

Schildkraut, Joellen ;

Pearce, C. Leigh ;

Chenevix-Trench, Georgia ;

Berchuck, Andrew ;

Pharoah, Paul D. P. .

CANCER RESEARCH, 2007, 67 (07) :3027-3035

[12] Polygenic susceptibility to breast cancer: current state-of-the-art [J].

Ghoussaini, Maya ;

Pharoah, Paul D. P. .

FUTURE ONCOLOGY, 2009, 5 (05) :689-701

[13] Candidate Gene Analysis Using Imputed Genotypes: Cell Cycle Single-Nucleotide Polymorphisms and Ovarian Cancer Risk [J].

Goode, Ellen L. ;

Fridley, Brooke L. ;

Vierkant, Robert A. ;

Cunningham, Julie M. ;

Phelan, Catherine M. ;

Anderson, Stephanie ;

Rider, David N. ;

White, Kristin L. ;

Pankratz, V. Shane ;

Song, Honglin ;

Hogdall, Estrid ;

Kjaer, Susanne K. ;

Whittemore, Alice S. ;

DiCioccio, Richard ;

Ramus, Susan J. ;

Gayther, Simon A. ;

Schildkraut, Joellen M. ;

Pharaoh, Paul P. D. ;

Sellers, Thomas A. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2009, 18 (03) :935-944

[14] Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway [J].

Hosgood, H. Dean, III ;

Menashe, Idan ;

Shen, Min ;

Yeager, Meredith ;

Yuenger, Jeff ;

Rajaraman, Preetha ;

He, Xingzhou ;

Chatterjee, Nilanjan ;

Caporaso, Neil E. ;

Zhu, Yong ;

Chanock, Stephen J. ;

Zheng, Tongzhang ;

Lan, Qing .

CARCINOGENESIS, 2008, 29 (10) :1938-1943

[15] Cyclin E in normal and neoplastic cell cycles [J].

Hwang, HC ;

Clurman, BE .

ONCOGENE, 2005, 24 (17) :2776-2786

[16]

KEYOMARSI K, 1994, CANCER RES, V54, P380

[17] Cyclin E and survival in patients with breast cancer. [J].

Keyomarsi, K ;

Tucker, SL ;

Buchholz, TA ;

Callister, M ;

Ding, Y ;

Hortobagyi, GN ;

Bedrosian, I ;

Knickerbocker, C ;

Toyofuku, W ;

Lowe, M ;

Herliczek, TW ;

Bacus, SS .

NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (20) :1566-1575

[18]

Lewis Cathryn M, 2002, Brief Bioinform, V3, P146, DOI 10.1093/bib/3.2.146

[19]

Liang YL, 2010, PLOS ONE, V5, DOI [10.1371/journal.pone.0012860, 10.1371/journal.pone.0015295]

[20] A novel interaction between HER2/neu and cyclin E in breast cancer [J].

Mittendorf, E. A. ;

Liu, Y. ;

Tucker, S. L. ;

McKenzie, T. ;

Qiao, N. ;

Akli, S. ;

Biernacka, A. ;

Liu, Y. ;

Meijer, L. ;

Keyomarsi, K. ;

Hunt, K. K. .

ONCOGENE, 2010, 29 (27) :3896-3907

← 1 2 3 4 →