Single nucleotide polymorphisms in nucleotide excision repair genes XPA, XPD, XPG and ERCC1 in advanced colorectal cancer patients treated with first-line oxaliplatin/fluoropyrimidine.
OBJECTIVE
Oxaliplatin damages the DNA, leading to apoptosis. XPA, XPD, ERCC1 and XPG genes are involved in DNA repair, and single nucleotide polymorphisms (SNPs) in these genes can influence the efficacy of oxaliplatin. We examined SNPs in these genes and correlated the results with time to progression (TTP), overall survival and response to oxaliplatin in 42 advanced colorectal cancer patients (CRC) treated with first-line oxaliplatin/fluoropyrimidine.


METHODS
DNA was obtained from peripheral blood cells, and the allelic discrimination assay was used to analyze the XPA 5'UTR T/C, XPD Lys751Gln, ERCC1 Lys259Thr and XPG, C/T.


RESULTS
Patients with XPG C/C genotype had a longer survival (p = 0.001) and TTP (p = 0.009) than patients with XPG C/T or T/T genotypes, and patients with both XPG C/C and XPA T/C or C/C genotypes had a longer survival (p = 0.0001) and TTP (p = 0.0001) than patients with other genotypes. XPG (CC) combined with XPA (TC/CC) genotypes showed an independent role for TTP (relative risk, RR = 6.38; p = 0.0001) and survival (RR = 34; p = 0.0005).


CONCLUSIONS
Polymorphism in XPG combined with XPA may be an important prognosticator of clinical outcome following oxaliplatin/ fluoropyrimidine chemotherapy. Further studies in larger patient cohorts are warranted to confirm their role in CRC.
Monzo
Mariano
M
Department of Human Anatomy and Embryology, University of Barcelona School of Medicine, Barcelona, Spain.
Moreno
Isabel
I
Navarro
Alfons
A
Ibeas
Rafael
R
Artells
Rosa
R
Gel
Bernat
B
Martinez
Francisco
F
Moreno
Jose
J
Hernandez
Raquel
R
Navarro-Vigo
Marta
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D000099250:DNA Excision Repair Protein ERCC-5
D000069287:Capecitabine; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D004720:Endonucleases; D005472:Fluorouracil; D009687:Nuclear Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D014157:Transcription Factors; D051760:Xeroderma Pigmentosum Group A Protein; D051759:Xeroderma Pigmentosum Group D Protein; D000099250:DNA Excision Repair Protein ERCC-5; C497314:XPA protein, human; C071447:ERCC1 protein, human; C497292:ERCC2 protein, human