Lys751Gln XPD and Arg399Gln XRCC1 in Romanians. Association with Sporadic Colorectal Cancer Risk and Different Stages of Carcinomas
L.M. Procopciuc, G. OsianOriginal article, no. 5, 2013
Background: DNA repair processes involved the removal ofmodified bases through the base excision repair (BER) pathwayand removal of damaged nucleotides through the nucleotideexcision repair (NER) pathways.Methods: in order to determine the association between XPD(Lys751Gln) and XRCC1 (Arg399Gln) SNPs and the risk ofCRC as well as tumor grade and stages in Romanians wegenotyped using PCR-RFLP methods 150 patients (80 femalesand 70 males) and 162 controls (100 females and 62 males).Results: The risk (odds ratio - OR) to develop sporadic CRC was3.02 (p=0.02) and 3.49 (p=0.001), respectively, in associationwith the homozygous Gln751 Gln751-XPD and Gln399 Gln399-XRCC1 genotypes. Higher risk for carriers of theGln751 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 observedin 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 Arg399Glnvariants to be on stage pT2 and pT4, respectively. Patientscarriers of Lys751Gln or Arg399Gln variants had 7.7-fold(p=0.002) and 18.94-fold (p 0.001) increased risk (OR) todevelop sporadic CRC in stage D.Conclusions: XPD and XRCC1 variants affect the risk forsporadic CRC in Romanians, seem to be associated with moreaggressive forms of sporadic CRC and may be prognosticfactors in patients with advanced CRC.
