Genetic variation in the major mitotic checkpoint genes and risk of breast cancer: a multigenic study on cancer susceptibility.
The mitotic checkpoint system is a mechanism essential for maintaining genomic stability and defects which have been linked to cancer development. We conducted this hospital-based case-control study to investigate whether genetic variants in three major spindle checkpoint genes (BUB3, MAD2L1, and BUB1) had any bearing on an individual risk of breast cancer (BC). A total of 462 incident BC patients and 529 cancer-free controls were enrolled in this study. Results showed that neither variants in BUB3 nor variants in MAD2L1 caused any significant effect on the risk of BC. However, the variant rs12623473 in BUB1 was significantly associated with increased BC risk with the odds ratio (OR) of 1.30 (95 % confidence interval (CI) 1.03-1.64) under the allelic model. The estimated population attributable risk of one copy of the risk allele for developing BC was 10.3 %. The bioinformatics analysis suggested that this variant may regulate the transcriptional ability of BUB1.
Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, 310009, Hangzhou, China.
Ping
P
Wang
Yong
Y
Wang
Haichao
H
Yan
Qiuping
Q
Xie
Liang
L
Zhao
Shaoming
S
Xu
Qunzi
Q
Zhao
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D064246:Mad2 Proteins / Q000235:genetics*; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C489444:BUB3 protein, human; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases