The c.*229C > T gene polymorphism in 3'UTR region of the topoisomerase IIβ binding protein 1 gene and LOH in BRCA1/2 regions and their effect on the risk and progression of human laryngeal carcinoma.
Topoisomerase IIβ binding protein 1 (TopBP1), a multiple-BRCT-domain, protein plays crucial roles in chromosome replication, DNA damage repair, apoptosis, and cell cycle checkpoint signalling. The aim of this study was to identify five SNPs at loci potentially located in the 3'UTR region of the TopBP1 gene (rs185903567, rs116645643, rs115160714, rs116195487, rs112843513), their relationship with the risk of squamous cell laryngeal cancer (SCLC), tumor invasiveness, and prognosis. Genotyping was performed in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Allele-specific TopBP1 mRNA and protein expressions were determined by using real-time PCR and Western blotting techniques, respectively. LOH in BRCA1/BRCA2 was determined by using microsatellite markers. Compared to homozygous common allele carriers, heterozygosity for the T variant was associated with increased risk of SCLC (adjusted odds ratio [OR] = 9.83, 95 % confidence interval [CI]: 3.12-22.16, p dominant < 0.0001). The presence of risk allele at rs115160714 TopBP1 determined a higher incidence of nodal metastases (OR = 7.98, 95 % CI: 3.94-16.00, p = 0.001) and higher tumor grade (OR = 6.48, 95 % CI: 0.86-48.01, p = 0.03). The heterozygotes displayed diffuse tumor growth with no distinct borderline (OR = 3.10, 95 % Cl: 0.92-10.62, p = 0.049) and higher depth of invasion (OR = 2.66, 95 % Cl: 0.78-9.03, p = 0.04). Relationships were also identified between TopBP1 mRNA/protein expression and overall survival (p < 0.0001). The incidence of LOH in BRCA1/BRCA2 was significantly related to higher tumor grade and TFG (p < 0.05). The results of this study suggest that rs115160714 TopBP1 may be a genetic marker of etiology and progression in laryngeal cancer.
I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153, Łódź, Poland. katarzyna.starska@umed.lodz.pl.
Katarzyna
K
Starska
Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236, Łódź, Poland.
Ewa
E
Forma
Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236, Łódź, Poland.
Maria
M
Nowacka-Zawisza
Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213, Łódź, Poland.
Iwona
I
Lewy-Trenda
Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236, Łódź, Poland.
Piotr
P
Ciesielski
I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153, Łódź, Poland.
Wioletta
W
Pietruszewska
Department of Otolaryngology, Żeromski Specialist Hospital, os. Na Skarpie 66, 31-913, Kraków, Poland.
Michał
M
Skóra
Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236, Łódź, Poland.
Magdalena
M
Bryś
D020413:3' Untranslated Regions; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D047368:Tumor Burden
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110513:TOPBP1 protein, human
BRCA1 and BRCA2 genes; Laryngeal cancer; Loss of heterozygosity (LOH); Single nucleotide polymorphism (SNP); TopBP1 gene/protein; Tumor front grading (TFG)