title: Topoisomerase IIβ binding protein 1 c.*229C>T (rs115160714) gene polymorphism and endometrial cancer risk.
abstract: TopBP1 (topoisomerase IIβ binding protein 1) protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. In this study we investigated whether alterations in the TopBP1 gene can influence the risk of endometrial cancer. We examined the association between five single nucleotide polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 3'UTR region of the TopBP1 gene and endometrial cancer risk as well as allele-specific gene expression. One hundred twenty-one endometrial cancer patients were genotyped for these SNPs. Allele-specific TopBP1 mRNA and protein expressions were determined by real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with endometrial cancer. Compared to homozygous common allele carriers, heterozygous for the T variant had significantly increased risk of endometrial cancer [adjusted odds ratio (OR) = 5.59, 95 % confidence interval (CI): 1.96-15.91, p = 0.0003]. Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT genotype. There was a significant association between the rs115160714 and tumor grade and FIGO classification. Most carriers of minor allele had a high grade tumors (G3) classified as FIGO III/IV. The results of our study raise a possibility that a genetic variation of TopBP1 may be implicated in the etiology of endometrial cancer.
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236, Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wójcik-Krowiranda
authors.forename: Paweł
authors.initials: P
authors.lastname: Jóźwiak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymczyk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bieńkiewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
authors.forename: Anna
authors.initials: A
authors.lastname: Krześlak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human