title: Coding region polymorphisms in the CHFR mitotic stress checkpoint gene are associated with colorectal cancer risk.
abstract: CHFR was recently identified as an early mitotic checkpoint that delays transition to metaphase in response to mitotic stress. Although studies have shown that CHFR is relevant to tumorigenesis, no previous report has investigated whether polymorphisms in the CHFR gene are associated with the risk of cancer development. Here, we genotyped polymorphisms in the CHFR gene and analyzed the possible associations of single polymorphisms and haplotypes with the risk and clinicopathological characteristics of colorectal cancer. Six coding SNPs in the CHFR gene were genotyped in 462 colorectal cancer patients and 245 healthy normal controls, using either the TaqMan assay or direct sequencing. Our results revealed that the V539M polymorphism was significantly associated with a lower risk of colorectal cancer (P=0.03; OR, 0.533; 95% CI, 0.302-0.94), and significantly correlated with no distant metastasis (M0 stage), different TNM stage, and microsatellite instability (MSI) among the colorectal cancer patients. Among the five tested haplotypes, hap 10 (TGACTA) was significantly associated with a lower risk of colorectal cancer (P=0.017; OR, 0.496; 95% CI, 0.279-0.883), and colorectal cancer patients carrying this haplotype showed no distant metastasis, different TNM stage, and microsatellite instability at a significantly higher frequency. These results reveal for the first time that polymorphisms in the CHFR gene are associated with colorectal cancer susceptibility.
authors: Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors: Hio Chung
authors: HC
authors: Kang
authors: Il-Jin
authors: IJ
authors: Kim
authors: Sang-Geun
authors: SG
authors: Jang
authors: Seung-Hyun
authors: SH
authors: Hong
authors: Jung-Ah
authors: JA
authors: Hwang
authors: Hai-Rim
authors: HR
authors: Shin
authors: Jae-Gahb
authors: JG
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053842:Microsatellite Instability; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases