Predictive effect of combined evaluation of XRCC1, XPD and GSTP1 single nucleotide polymorphisms in platinum based chemotherapy

Objective To investigate the predictive value of combined analysis on single nucleotide polymorphisms (SNPs) of X-ray cross-complementing1 ( XRCC1 ) gene 194 and 399 codon,xeroderma pigmentosum group D (XPD) gene 312 codon and glutathione S-transferase P1 (GSTP1) gene 105 codon in platinum based chemotherapy.Methods Direct sequencing was performed to detect XRCC1,XPD and GSTP1 genotypes in peripheral blood from 50 cancer patients receiving platinum-based chemotherapy.Genetic polymorphisms of these genes related to sensitivity of platinum were reviewed.Results Favorable genotypes were Arg/Trp and Trp/Trp in XRCC1 194 codon,Arg/Arg in XRCC1 399 codon,Asn/Asn in XPD 312 codon and Val/Val in GSTP1 105 codon.The response rate to chemotherapy was 57.1％,75.0％,60.9％,85.7％ and 87.5％,respectively.The response rate for patients possessing ≥2 favorable genotypes and those possessing 1 or 0 favorable genotype was 78.9％,36.4％ and 0,respectively.Patients possessing ≥2 favorable genotypes demonstrated higher sensitivity to platinum based chemotherapy,compared with those possessing 1 or 0 favorable genotype ( x2 =25.79,P ＜ 0.01 ).Conclusions Combination analysis of genomic polymorphisms of XRCC1,XPD and GSTP1 may be useful in predicting sensitivity of platinum based chemotherapy. Key words: DNA-binding proteins/GE ; Xeroderma pigmentosum group D protein/GE;  Glutathione transferase/GE ;  Organoplatinum compounds/AE;  Drug screening assays, antitumor