Abstract
We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypes and survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinese patients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatment from January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)=2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR (95% CI)=1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)=0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD 751Lys/Lys [HR (95% CI)=0.51(0.33-0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely to benefit from 5-FU/oxalipatin chemotherapy.
Highlights
Colorectal cancer is the third most common cancer diagnosed in the world and the leading cause of cancer death in western industrialized countries (IARC, 2008)
Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method
We found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR= 2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR= 1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR= 0.66(0.360.95)]
Summary
Colorectal cancer is the third most common cancer diagnosed in the world and the leading cause of cancer death in western industrialized countries (IARC, 2008) Genetic susceptibility to this disease may result from inherited mutations in genes involved in carcinogenesis. Deficit of adequate function of DNA repair gene could accelerate genetic instability and the rate of genetic change, and enhance the probability of carcinogenesis (Mohrenweiser and Jones, 1998; Shilds and Harris, 2000). These DNA repair genes are reported that they have a role in the prognosis of colorectal cancer. Single nucleotide polymorphism of genes involved in the NER pathway affects DNA repair capacity, and influences the prognosis of malignant diseases (Zhou et al, 2004; Handra-Luca et al, 2007; McWilliams et al, 2008; Shore et al, 2008; Chang et al, 2009)
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