title: MCPH1 protein expression and polymorphisms are associated with risk of breast cancer.
abstract: Microcephalin 1 (MCPH1) has a crucial role in the DNA damage response by promoting the expression of checkpoint kinase 1 (CHK1) and breast cancer susceptibility gene 1 (BRCA1). MCPH1 containing BRCT domain has been suggested as a tumor suppressor in breast and ovarian cancers. We analyzed the effect of both protein expression and MCPH1 polymorphisms in breast cancer patients. Low nuclear expression of microcephalin was present in 52.4% of breast cancers and was associated with allele T in rs2912010 (p=0.046). However, cytoplasmic microcephalin expression increased with increasing grade (p=0.010). An association between low nucleus microcephalin expression and allele T was identified in rs2912010 (p=0.046). After data analysis, allele distribution of the MCPH1 polymorphisms was not different between breast cancer patients and healthy controls. But the polymorphism was associated with negative status for ER (rs2912010/C2302T; p=0.032, rs1057090/C2358T; p=0.027, rs2912016/C2494A; p=0.024), and allele T in both rs2912010 and rs1057090 was associated with increasing tumor grade (rs2912010; p=0.040, rs1057090; p=0.043) in breast cancer. We are first to report that association of MCPH1 protein expression and its polymorphisms in breast cancer. The MCPH1 polymorphisms and protein expression were associated with tumorigenesis in breast cancer and may be a useful biomarker for identification of the aggressive types of breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 project), School of medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Yong Hwa
authors.initials: YH
authors.lastname: Jo
authors.forename: Hye Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Juhie
authors.initials: J
authors.lastname: Lee
authors.forename: Sang Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Cho
authors.forename: In Sug
authors.initials: IS
authors.lastname: Kang
authors.forename: Won Jae
authors.initials: WJ
authors.lastname: Choe
authors.forename: Hyung Hwan
authors.initials: HH
authors.lastname: Baik
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics; D056910:Republic of Korea
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen