association of germline variation in ccne1 and cdk2 with breast cancer risk, progression and survival among chinese han women生殖系协会ccne1 cdk2与乳腺癌风险的变化,发展和生存在中国汉族女性.pdf

Association of Germline Variation in CCNE1 and CDK2 with Breast Cancer Risk, Progression and Survival among Chinese Han Women 1 1 2 1 1 1 1 Ji-Yuan Han , Hui Wang , Yun-Tao Xie , Yan Li , Li-Yuan Zheng , Yuan Ruan , Ai-Ping Song , Xin- 1 1 Xia Tian *, Wei-Gang Fang * 1 Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’ Republic of China, 2 Breast Center, Peking University School of Oncology, Beijing Cancer Hospital Institute, Beijing, People’ Republic of China Abstract 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 loc