Polymorphisms In XPD751 Gene And Sensitivity To Platin-based Chemotherapy In Lung Cancer

[Objective]XPD751 polymorphisms,may be associated to nucleotide excision repair,then influence the sensitivity to platinum-based chemotherapy.This study is to investigate the relationship between polymorphisms of DNA repair gene XPD751 and sensitivity to platinumbased chemotherapy in lung cancer through detecting XPD751 genotypes by PCR-RFLP.[Methods]234 lung cancer samples were collected from patients with histologically confirmed lung cancer.All patients were treated with platinum-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy.XPD751 genotypes were detected by PCR-RFLP method.The forward primer:5'-CCTCTCCCTTTCCTCTG TTC-3' and reverse primer:5'-CAGGTGAGGGGGACATCT-3' were used to amplify the genomic XPD751 gene of participants.PCR was carried out in a final volume of 25μl containing 0.5μL of genomic DNA,2.5μL of dATP,dTTP,dCTP,and dGTP,1.0μL each primer (10 pmol/μL),1 units of Taq polymerase(Biotools),2.5μL of 10×Buffer and 1.5μL of MgCl2.for 5 minutes at 95℃followed by 35 cycles of 30 seconds at 95℃,30 seconds at 60℃,30 seconds at 72℃, and a final extension of 7 minutes at 72℃.PCR products were digested for 2 hours with the MboⅡenzyme at 37℃.DNA fragments were electrophoresed on agarose gels(2%)and visualised by ethidium bromide staining.All analyses were performed with SAS.The differences in the chemosensitivity of each genotype were detected by using the x~2 test. Unconditional logistic regression were used to adjust odds ratio(OR)and 95%confidence interval(CI)for the matching variables.[Results]1)Of all cases,the frequencies of XPD751 Lys/Lys, Lys/Gln and Gin/Gin genotype were 82.1%,17.1%and 0.8%, respectively.The overall response rate of platinum-based chemotherapy in all of patients was 47.0%.2)The response rate of chemotherapy among patients with XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotype was 50.0%,30.0%,100%,respectively,being a significant difference, x~2=7.59,P=0.0225.After adjusting the influencing factors of gender, age,clinical stage,cytology type,chemotherapy regimens,we found that the probability of chemotherapy woke on patients with Lys/Lys genotype 2.28-fold to that in patients with Lys/Gln genotype,OR=2.28,95%CI: 1.05～4.91.3)The incidence rate of vomiting/nausea and alopecie in Lys/Lys genotype was significantly higher than other genotypes,x~2 =4.504,P=0.034;x~2=4.011,P=0.045.[Conclusion]These results suggest that the polymorphisms of the XPD75 lcorrelates with clinical response to platinum-based chemotherapy,and the XPD751 genotypes detected by PCR-RFLP method may identify lung cancer patients with responsive to platinum-based chemotherapy.