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Relationship between DNA repair gene XPD751 single-nucleotide polymorphisms and prognosis of colorectal cancer

Author(s): Y. Dong, J.W. Liu, Y.J. Gao, T. Zhou and Y.M. Chen

We examined the relationships between singlenucleotide polymorphisms (SNPs) in the DNA repair gene XPD751 and the efficacy and time to disease progression (TTP) in colorectal cancer patients after platinum-based chemotherapy. Ninety-eight patients diagnosed with advanced colorectal cancer were subjected to oxaliplatin and 5-fluorouracil combination therapy. DNA was extracted from venous blood before chemotherapy. Polymerase chain reactionrestriction fragment length polymorphism analysis was used to detect XPD751 SNPs. The relationship between genotypes and prognosis was compared. The frequencies of the XPD751 Lys/Lys, Lys/Gln, and Gln/Gln genotypes were 76 (77.55%), 17 (17.35%), and 5 (5.10%), respectively. The efficiency of XPD751 Lys/Lys, Lys/Gln and Gln/Gln genotypes were 50.00, 29.41, and 20%, respectively. The efficiency rate between XPD751 Lys/Lys and Lys/Gln showed a significant difference (c² = 4.04, P < 0.05). After adjusting for gender, age, and metastasis location, chemotherapy failure in patients carrying XPD751 Lys/Gln was 3.404-fold higher than in patients carrying the Lys/ Lys genotype. Median TTP was 304 days (10.1 months) and median TTP in patients with XPD751 Lys/Lys and ≥1 Gln genotype was 340 and 87 days. After comparing TTP in patients carrying Lys/Lys and patients carrying ≥1 Gln, the difference was significant. SNPs in the DNA repair gene XPD751 may be associated with oxaliplatin and 5-fluorouracil chemotherapy sensitivity in colorectal cancer patients. These polymorphisms may be associated with TTP in patients with advanced colorectal cancer after first-line chemotherapy of oxaliplatin. XPD751 SNPs may be predictive factors of prognosis in colorectal cancer patients receiving oxaliplatin and 5-fluorouracil chemotherapy.