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Tagging Snps in the Excision Repair Cross-Complementing Group 4 (ERCC4)Gene Increased Risk of Cervical Squamous Cell Carcinoma (CSCC) and Modulate the Disease Outcome
Edyta Pawlak-Adamska, Magdalena Bartosinska, Iwona Wlodarska-Polinska, Agnieszka Ignatowicz-Pacyna, Jan Kornafel, Marcin Stepien, Iwona Ewa Kochanowska and Irena Frydecka
Background: Given the important role of ERCC4 gene in multiple DNA repair systems, we hypothesized that genetic variations within this gene may be a cervical squamous cell carcinoma (CSCC) risk and disease modulatory factor.
Methods: In population-based, case-control association study including 143 CSCC patients and 207 healthy women, two ERCC4tagSNPs were studied.
Results: A significant protective effect against CSCC was observed assuming a dominant model in case of ERCC4rs3136176 ([AA]+[AT]vs.[TT]: p=0.04,OR=0.43), and genotype [AA] strongly protects against poorly (G3) differentiated CSCC (pcorreced=0.008,OR=0.15) and significantly increased the disease remission rate (p=0.05,OR=0.48).
A statistically significant increase frequency of ERCC4rs1799798 [A] allele was seen in patients with well differentiated (G1) CSCC (p=0.02, OR=2.40). Contrary, an opposite trend was observed when G1 was compared with G2 (moderately differentiated) CSCC (p=0.06). Furthermore, ERCC4rs1799798 [A] allele tended to be increased in patients with carcinoma planoepitheliale keratodes (Cpk) (p=0.07).
Haplotype ERCC4rs3136176[A]/ERCC4rs1799798[G] significantly decreased risk of G1 as well as G3 CSCC (p=0.02,OR=0.50, and p=0.017,OR=0.42, respectively) and only tended to decrease risk of CSCC (p=0.07,OR=0.758) as well as carcinoma planoepitheliale akeratodes (Cpa) (p=0.059,OR=0.71).
In contrast haplotype AA significantly increased risk of G1 CSCC and risk of Cpk (p=0.01, OR=2.51, and p=0.049, OR=1.96, respectively), whereas haplotype TG increased risk of G3 CSCC (p=0.037, OR=2.17).
The overall survival rates showed similar mean survival rates according to patients' genotypes at both studied SNPs.
Conclusion: The above findings consistently suggested that genetic variants in ERCC4 gene may play significant role in CSCC pathophysiology.