RGD Reference Report - ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin. - Rat Genome Database

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ERCC1/BRCA1 expression and gene polymorphisms as prognostic and predictive factors in advanced NSCLC treated with or without cisplatin.

Authors: Tiseo, M  Bordi, P  Bortesi, B  Boni, L  Boni, C  Baldini, E  Grossi, F  Recchia, F  Zanelli, F  Fontanini, G  Naldi, N  Campanini, N  Azzoni, C  Bordi, C  Ardizzoni, A  Bio-FAST trial group,  
Citation: Tiseo M, etal., Br J Cancer. 2013 Apr 30;108(8):1695-703. doi: 10.1038/bjc.2013.127. Epub 2013 Apr 2.
RGD ID: 127229950
Pubmed: PMID:23549037   (View Abstract at PubMed)
PMCID: PMC3669730   (View Article at PubMed Central)
DOI: DOI:10.1038/bjc.2013.127   (Journal Full-text)


BACKGROUND: The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.
METHODS: Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.
RESULTS: Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).
CONCLUSION: This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung non-small cell carcinoma disease_progressionIEP 127229950 RGD 
lung non-small cell carcinoma disease_progressionISOERCC1 (Homo sapiens)127229950; 127229950 RGD 
lung non-small cell carcinoma treatmentIAGP 127229950DNA:missense mutation:p.R399Q (human)RGD 
lung non-small cell carcinoma treatmentISOXRCC1 (Homo sapiens)127229950; 127229950DNA:missense mutation:p.R399Q (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ercc1  (ERCC excision repair 1, endonuclease non-catalytic subunit)
Xrcc1  (X-ray repair cross complementing 1)

Genes (Mus musculus)
Ercc1  (excision repair cross-complementing rodent repair deficiency, complementation group 1)
Xrcc1  (X-ray repair complementing defective repair in Chinese hamster cells 1)

Genes (Homo sapiens)
ERCC1  (ERCC excision repair 1, endonuclease non-catalytic subunit)
XRCC1  (X-ray repair cross complementing 1)


Additional Information