Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women.
Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women.
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DOI：
10.1371/journal.pone.0049296
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fang WG
中科院分区：
文献类型：
--
作者：
Han JY;Wang H;Xie YT;Li Y;Zheng LY;Ruan Y;Song AP;Tian XX;Fang WG
细胞周期蛋白依赖性激酶2 (CDK2)-细胞周期蛋白E复合物的体细胞改变已被证明有助于乳腺癌（BC）的发生和进展。本研究旨在探讨CDK2和CCNE1（一种编码G1/S特异性细胞周期蛋白E1的基因，以前称为细胞周期蛋白E）的单核苷酸多态性（snp）对中国汉族人群BC风险、进展和生存的影响。我们在1207例BC病例和1207例年龄匹配对照中对CCNE1的6个单倍型标记snp （htsnp）和CDK2的2个单倍型标记snp （htsnp）进行了基因分型，然后根据我们的基因分型数据和这些单倍型标记snp的连锁不平衡状态重建了单倍型块。对于CCNE1，三个htsnp的次要等位基因纯合子与BC风险相关（rs3218035：校正优势比[aOR] = 3.35, 95%可信区间[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），这三个位点在增加BC风险方面呈剂量依赖性（P趋势= 0.0001）。此外，5 snp单倍型CCGTC不携带3个高危snp的次要等位基因，与有利的无事件生存相关（风险比[HR] = 0.53, 95% CI = 0.32-0.90）。分层分析表明，rs3218038小等位基因纯合子携带者在侵袭性肿瘤患者中的无事件生存率较差（肿瘤大小为> ~ 2cm组：HR = 2.06, 95% CI = 1.06 ~ 3.99；淋巴结转移阳性组：HR = 2.41, 95% CI = 1.15 ~ 5.03； ii ~ iv期组：HR = 2.03, 95% CI = 1.09 ~ 3.79）。对于CDK2，没有发现显著的关联。本研究提示CCNE1基因变异可能与中国汉族人群BC风险和生存有关。它们可能成为个体评估BC易感性和预后的分子标记。然而，还需要进一步的验证研究。
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. 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. 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.
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影响因子：
4.7
作者：
Driver KE;Song H;Lesueur F;Ahmed S;Barbosa-Morais NL;Tyrer JP;Ponder BA;Easton DF;Pharoah PD;Dunning AM;Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
通讯作者：
Studies in Epidemiology and Risks of Cancer Heredity (SEARCH) Team
细胞周期基因和卵巢癌易感性：tagSNP 分析。
影响因子：
8.8
作者：
Cunningham, J. M.;Vierkant, R. A.;Sellers, T. A.;Phelan, C.;Rider, D. N.;Liebow, M.;Schildkraut, J.;Berchuck, A.;Couch, F. J.;Wang, X.;Fridley, B. L.;Gentry-Maharaj, A.;Menon, U.;Hogdall, E.;Kjaer, S.;Whittemore, A.;DiCioccio, R.;Song, H.;Gayther, S. A.;Ramus, S. J.;Pharaoh, P. D. P.;Goode, E. L.
通讯作者：
Goode, E. L.
影响因子：
5.2
作者：
Berulava, Tea;Horsthemke, Bernhard
通讯作者：
Horsthemke, Bernhard
影响因子：
7.3
作者：
Ruan, Yuan;Song, Ai-Ping;Fang, Wei-Gang
通讯作者：
Fang, Wei-Gang
影响因子：
4
作者：
Schork, Nicholas J.;Murray, Sarah S.;Frazer, Kelly A.;Topol, Eric J.
通讯作者：
Topol, Eric J.