RGD Reference Report - The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens. - Rat Genome Database

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The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens.

Authors: Artac, Mehmet  Bozcuk, Hakan  Pehlivan, Sacide  Akcan, Songül  Pehlivan, Mustafa  Sever, Tugce  Ozdogan, Mustafa  Savas, Burhan 
Citation: Artac M, etal., J Cancer Res Clin Oncol. 2010 Jun;136(6):803-9. doi: 10.1007/s00432-009-0720-3. Epub 2009 Nov 12.
RGD ID: 150573820
Pubmed: PMID:19908066   (View Abstract at PubMed)
DOI: DOI:10.1007/s00432-009-0720-3   (Journal Full-text)


BACKGROUND: Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC).
METHODS: We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR-RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated.
RESULTS: In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes.
CONCLUSIONS: XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC1Humancolorectal adenocarcinoma treatmentIAGP associated with Neoplasm Metastasis more ...RGD 
Xrcc1Ratcolorectal adenocarcinoma treatmentISOXRCC1 (Homo sapiens)associated with Neoplasm Metastasis more ...RGD 
Xrcc1Mousecolorectal adenocarcinoma treatmentISOXRCC1 (Homo sapiens)associated with Neoplasm Metastasis more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XRCC1HumanNeoplasm of the large intestine treatmentIAGP DNA:missense mutation:cds: p.R399Q and c.1196G>A (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Xrcc1  (X-ray repair cross complementing 1)

Genes (Mus musculus)
Xrcc1  (X-ray repair complementing defective repair in Chinese hamster cells 1)

Genes (Homo sapiens)
XRCC1  (X-ray repair cross complementing 1)


Additional Information