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

  • Epidemiology
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Abstract

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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No 81171961) and Doctoral Fund of Ministry of Education of China (No 20110001110060).

Conflict of interest

We declare no conflict of interest.

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Authors and Affiliations

  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, China

    Hui Wang, Ji-Yuan Han, Yuan Ruan, Ai-Ping Song, Li-Yuan Zheng, Wei-Zao Zhang, Yan Li, Xin-Xia Tian & Wei-Gang Fang

  2. Breast Center, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, 100142, China

    Yun-Tao Xie

  3. Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 52a, 6020, Innsbruck, Austria

    Constantin Sajdik

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  1. Hui Wang
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Correspondence to Xin-Xia Tian or Wei-Gang Fang.

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Wang, H., Xie, YT., Han, JY. et al. Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population. Breast Cancer Res Treat 136, 241–251 (2012). https://doi.org/10.1007/s10549-012-2244-9

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  • DOI: https://doi.org/10.1007/s10549-012-2244-9

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