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Genetic variation in DNA repair genes: ERCC4 and XRCC3 and cervical squamous cell carcinoma risk

Edyta A. Pawlak-Adamska1*, Magdalena Bartosinska1, Iwona Wlodarska-Polinska2, Agnieszka Ignatowicz-Pacyna3, Jan Kornafel3 and Irena Frydecka1
  • 1 Institute of Immunology & Experimental Therapy, Experimental Therapy, Poland
  • 2 EuroMedic Poland, International Oncological Center, Poland
  • 3 Medical University, Department of Oncology and Gynaecological Oncology Clinic, Poland

As reduced DNA repair capacity may lead to genetic instability and carcinogenesis, genes involved in DNA repair have been proposed as candidate cancer susceptibility genes including in cervical cancer.
ERCC4 (XPF) is one of central players in the NER, which counteracts the consequences of mutagenic exposure of cell. XRCC3 is known to participate in homologous recombination to maintain chromosome stability and repair DNA damage.
We investigated 4 tagSNPs in 2 DNA repair genes - ERCC4: rs3136176, rs1799798 and XRCC3: rs3212079, rs3212102 in 132 cervical squamous cell carcinoma (CSCC) patients and 196 healthy controls.
In single SNP analyses, we found that among studied SNPs 3 were directly associated with risk of CSCC: ERCC4rs3136176 and in XRCC3: rs3212079, rs3212102. With respect to ERCC4 SNP, we found that carriers of [TT] genotype was 2.82 more prone to CSCC (p=0.01, 95%CI:1.21-6.59).
With respect to XRCC3 SNPs, presence of rs3212102[CC] genotype 2.18 increased risk of cancer (p=0.04, 95%CI:1.03-4.65) and rs3212079[A] allele (genotype [AA] and/or [GA]) 2.37 increased risk of CSCC (p=0.006, 95%CI:1.27-4.42).
Haplotype XRCC3rs3212079[A]/XRCC3rs3212102[C] significantly increased risk of CSCC (p=0.0007).
Using multivariate logistic regression analysis, 3 of the investigated SNPs: ERCC4rs3136176, XRCC3rs3212079 and XRCC3rs3212102 showed a significant association with CSCC risk in the over all population.
Moreover, haplotype XRCC3rs3212079[A]/XRCC3rs3212102[C] showed a tendency to be more frequent in patients with carcimona planoepitheliale akeratodes (Cpa) as compared with keratodes type (Cpk) (p=0.07) and haplotype XRCC3rs3212079[G]/XRCC3rs3212102[C] showed an opposite tendency (p=0.07). None of studied SNPs were associated with grading or staging.

References

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Keywords: CSCC, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Cancer, DNA repair gene

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune-mediated disease pathogenesis

Citation: Pawlak-Adamska EA, Bartosinska M, Wlodarska-Polinska I, Ignatowicz-Pacyna A, Kornafel J and Frydecka I (2013). Genetic variation in DNA repair genes: ERCC4 and XRCC3 and cervical squamous cell carcinoma risk. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00636

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Received: 13 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Edyta A Pawlak-Adamska, Institute of Immunology & Experimental Therapy, Experimental Therapy, Wroclaw, Lower Silesia, 53-114, Poland, edyta.pawlak@hirszfeld.pl