Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer.
BACKGROUND
Platinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel-cisplatin-treated stage IV NSCLC patients.


METHODS
Using the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 -37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel-cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR.


RESULTS
Overall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for 11 patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC1 118 genotype (P=0.03). No other significant differences were observed.


CONCLUSIONS
Patients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.
Hospital Clinico Lozano Blesa, Zaragoza, Spain.
D
D
Isla
C
C
Sarries
R
R
Rosell
G
G
Alonso
M
M
Domine
M
M
Taron
G
G
Lopez-Vivanco
C
C
Camps
M
M
Botia
L
L
Nuñez
M
M
Sanchez-Ronco
J J
JJ
Sanchez
M
M
Lopez-Brea
I
I
Barneto
A
A
Paredes
B
B
Medina
A
A
Artal
P
P
Lianes
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018736:DNA Adducts; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077143:Docetaxel; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D018736:DNA Adducts; D004268:DNA-Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin