studies, polymorphism analysis of genes of this system, including ERCC4 (cytogenetic location: chromosome 16p13.12) and XRCC3 (cytogenetic location:.
ERCC4 and XRCC3 tagSNPs association with cervical squamous cell carcinoma (CSCC) development and clinical outcome in Polish population 1
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3
Edyta A. Pawlak-Adamska , Magdalena Bartosinska1, Lidia Karabon, Iwona Wlodarska-Polinska , Barbara Izmajlowicz , 3 3 3 1, 3 Agnieszka Ignatowicz-Pacyna , Jan Kornafel , Marcin Stepien , Irena Frydecka Rafal Matkowski 1
Laboratory of Immunopathology, Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, Poland 2 Euromedic Oncotherapy Walbrzych Poland, Sokolowskiego 4, 58-309 Walbrzych, Poland 3 Department of Oncology and Gynecological Oncology Clinic, Medical University, Wroclaw, Poland
Introduction: DNA repair system, one of main player in cancer biology, are responsible for maintaining the integrity and stability of the genome. In addition to expression studies, polymorphism analysis of genes of this system, including ERCC4 (cytogenetic location: chromosome 16p13.12) and XRCC3 (cytogenetic location: chromosome 14q32.33) (Fig. 1.), can determine whether germline allelic variants are linked to cancer susceptibility and/or clinical outcome by affecting the function of their protein products. Fig. 2. ERCC4rs3136176, XRCC3rs3212079 and XRCC3rs3212102 genotype frequencies in cancer-free healthy women (Controls) and squamous cell cervical cancer (CSCC) patients.
Materials and methods: In population-based, case-control association study in 350 Polish Caucasian women, including 143 cervical squamous cell carcinoma (CSCC) patients, two ERCC4tagSNPs (rs3136176, rs1799798) and seven XRCC3tagSNPs (rs3212079, rs3212102, rs861534, rs861537, rs709399, rs12432907, rs1799796) were genotyped. Statistical analysis was stratified according to grading, FIGO, histological subtypes and response to treatment. Combined effects of all studied genetic marker on the development of CSCC were analyzed by multivariate logistic regression analysis employing a quasi-Newton TM estimation method (Epi Info 7.1.1.14 free software). The significance of genetic factors (defined as combined effects of two from all studied) affecting the development of CSCC was assessed employing the Svejgaard and Ryder method: for each comparison the Odds Ratio (OR) was calculated by Haldane's modification of Woolf's methods and p-values were
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100 80
CSCC 60
Controls
ERCC4 gene
40
2
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20 0 T] A [ ]+
AA
[
] [TT [A
ERCC4rs3136176
GA ]+[
]
A
G] [G
[T
XRCC3rs3212079
T] C [ T]+
C] [C
XRCC3 gene
XRCC3rs3212102
1 - p= 0.04, OR= 0.43, 95%CI:0.19-0.99 2 - p= 0.0002, OR= 3.30, 95%CI:1.73-6.32 3 - p= 0.04, OR= 0.50, 95%CI:0.25-0.97 * p-value after Yate's correction
Fig. 3. ERCC4rs3136176 genotype frequencies in cancer-free healthy women (Controls) and squamous cell cervical cancer (CSCC) well (G1), moderately (G2) and poorly (G3) differentiated patients.
Fig. 4. ERCC4rs3136176 genotype frequencies in cancer-free healthy women (Controls) and squamous cell cervical cancer (CSCC) with disease remission (CR) and disease progression (PD).
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assessed by Fisher's exact test were estimated using the MultiGenBank platform ImGen analysis module (www.mutligenbank.pl). p
