title: Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population.
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.
authors.affiliation: 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, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Xie
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Han
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ruan
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Song
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Zheng
authors.forename: Wei-Zao
authors.initials: WZ
authors.lastname: Zhang
authors.forename: Constantin
authors.initials: C
authors.lastname: Sajdik
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xin-Xia
authors.initials: XX
authors.lastname: Tian
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Fang
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D000072379:NIMA-Related Kinases; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: C507203:CNTROB protein, human; D018797:Cell Cycle Proteins; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases