title: Association between the c.*229C>T polymorphism of the topoisomerase IIβ binding protein 1 (TopBP1) gene and breast cancer.
abstract: Topoisomerase IIβ binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 3'UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific TopBP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95% confidence interval: 1.63-8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer.
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzeziańska
authors.forename: Anna
authors.initials: A
authors.lastname: Krześlak
authors.forename: Grażyna
authors.initials: G
authors.lastname: Chwatko
authors.forename: Paweł
authors.initials: P
authors.lastname: Jóźwiak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymczyk
authors.forename: Beata
authors.initials: B
authors.lastname: Smolarz
authors.forename: Hanna
authors.initials: H
authors.lastname: Romanowicz-Makowska
authors.forename: Waldemar
authors.initials: W
authors.lastname: Różański
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human