Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population

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• 作者：Hui Wang (1)
  Yun-Tao Xie (2)
  Ji-Yuan Han (1)
  Yuan Ruan (1)
  Ai-Ping Song (1)
  Li-Yuan Zheng (1)
  Wei-Zao Zhang (1)
  Constantin Sajdik (3)
  Yan Li (1)
  Xin-Xia Tian (1) tianxinxia@yahoo.com
  Wei-Gang Fang (1) wgfang@bjmu.edu.cn
• 关键词：Centrobin Nek2 – ; Single nucleotide polymorphism – ; Haplotype – ; Breast cancer
• 刊名：Breast Cancer Research and Treatment
• 出版年：2012
• 出版时间：November 2012
• 年：2012
• 卷：136
• 期：1
• 页码：241-251
• 全文大小：297.4 KB
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• 作者单位：1. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sino-Austrian Center for Biomarker Discovery, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191 China2. Breast Center, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, 100142 China3. Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 52a, 6020 Innsbruck, Austria
• ISSN：1573-7217

文摘

Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09–0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18–2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97–14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.