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  • Title: Lys751Gln XPD and Arg399Gln XRCC1 in Romanians. Association with sporadic colorectal cancer risk and different stages of carcinomas.
    Author: Procopciuc LM, Osian G.
    Journal: Chirurgia (Bucur); 2013; 108(5):711-8. PubMed ID: 24157118.
    Abstract:
    BACKGROUND: DNA repair processes involved the removal of modified bases through the base excision repair (BER) pathway and removal of damaged nucleotides through the nucleotide excision repair (NER) pathways. METHODS: in order to determine the association between XPD(Lys751Gln) and XRCC1 (Arg399Gln) SNPs and the risk of CRC as well as tumor grade and stages in Romanians we genotyped using PCR-RFLP methods 150 patients (80 females and 70 males) and 162 controls (100 females and 62 males). RESULTS: The risk (odds ratio - OR) to develop sporadic CRC was 3.02 (p=0.02) and 3.49 (p=0.001), respectively, in association with the homozygous Gln751 Gln751-XPD and Gln399 Gln399-XRCC1 genotypes. Higher risk for carriers of the Gln751 Gln751 - Arg399 Arg399 (OR 4.19, p=0.027),Gln399 Gln399 - Lys751 Lys751 (OR 3.21, p=0.013),Gln399 Gln399 - Lys751 Gln751 (OR 4.5, p=0.05),Lys751 Gln751 - Arg399 Gln399 (OR 3.94, p 0.001) combined genotypes was observed. The lowest risk was observed in carriers of Lys751 Lys751-Arg399 Arg399 genotypes (OR0.24, p 0.001). 2.24-fold (p=0.05) and 3.75-fold (p=0.004)increased risk (OR) for carriers of the Lys751Gln or Arg399Gln variants to be on stage pT2 and pT4, respectively. Patients carriers of Lys751Gln or Arg399Gln variants had 7.7-fold(p=0.002) and 18.94-fold (p 0.001) increased risk (OR) to develop sporadic CRC in stage D. CONCLUSIONS: XPD and XRCC1 variants affect the risk for sporadic CRC in Romanians, seem to be associated with more aggressive forms of sporadic CRC and may be prognostic factors in patients with advanced CRC.
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