Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients

R. de las Peñas, M. Sanchez-Ronco, V. Alberola, M. Taron, C. Camps, R. Garcia-Carbonero, B. Massuti, C. Queralt, M. Botia, R. Garcia-Gomez, D. Isla, M. Cobo, M. Santarpia, F. Cecere, P. Mendez, J. J. Sanchez, R. Rosell

Research output: Contribution to journalArticle

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Abstract

Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/ gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

Original languageEnglish
Pages (from-to)668-675
Number of pages8
JournalAnnals of Oncology
Volume17
Issue number4
DOIs
Publication statusPublished - Apr 2006

Fingerprint

gemcitabine
Non-Small Cell Lung Carcinoma
DNA Repair
Cisplatin
X-Rays
Survival
Xeroderma Pigmentosum
Genes
Genotype
Malignant Pleural Effusion
Ribonucleotide Reductases
Peroxisome Proliferator-Activated Receptors
Genetic Polymorphisms
Cyclooxygenase 2
Ligases
Proportional Hazards Models
Epidermal Growth Factor
Interleukin-6
Lung Neoplasms
Odds Ratio

Keywords

  • Cisplatin
  • DNA repair genes
  • Gemcitabine
  • Non-small-cell lung cancer
  • Polymorphisms
  • XRCC3

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

de las Peñas, R., Sanchez-Ronco, M., Alberola, V., Taron, M., Camps, C., Garcia-Carbonero, R., ... Rosell, R. (2006). Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients. Annals of Oncology, 17(4), 668-675. https://doi.org/10.1093/annonc/mdj135

Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients. / de las Peñas, R.; Sanchez-Ronco, M.; Alberola, V.; Taron, M.; Camps, C.; Garcia-Carbonero, R.; Massuti, B.; Queralt, C.; Botia, M.; Garcia-Gomez, R.; Isla, D.; Cobo, M.; Santarpia, M.; Cecere, F.; Mendez, P.; Sanchez, J. J.; Rosell, R.

In: Annals of Oncology, Vol. 17, No. 4, 04.2006, p. 668-675.

Research output: Contribution to journalArticle

de las Peñas, R, Sanchez-Ronco, M, Alberola, V, Taron, M, Camps, C, Garcia-Carbonero, R, Massuti, B, Queralt, C, Botia, M, Garcia-Gomez, R, Isla, D, Cobo, M, Santarpia, M, Cecere, F, Mendez, P, Sanchez, JJ & Rosell, R 2006, 'Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients', Annals of Oncology, vol. 17, no. 4, pp. 668-675. https://doi.org/10.1093/annonc/mdj135
de las Peñas R, Sanchez-Ronco M, Alberola V, Taron M, Camps C, Garcia-Carbonero R et al. Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients. Annals of Oncology. 2006 Apr;17(4):668-675. https://doi.org/10.1093/annonc/mdj135
de las Peñas, R. ; Sanchez-Ronco, M. ; Alberola, V. ; Taron, M. ; Camps, C. ; Garcia-Carbonero, R. ; Massuti, B. ; Queralt, C. ; Botia, M. ; Garcia-Gomez, R. ; Isla, D. ; Cobo, M. ; Santarpia, M. ; Cecere, F. ; Mendez, P. ; Sanchez, J. J. ; Rosell, R. / Polymorphisms in DNA repair genes modulate survival in cisplatin/ gemcitabine-treated non-small-cell lung cancer patients. In: Annals of Oncology. 2006 ; Vol. 17, No. 4. pp. 668-675.
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abstract = "Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/ gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.",
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AU - de las Peñas, R.

AU - Sanchez-Ronco, M.

AU - Alberola, V.

AU - Taron, M.

AU - Camps, C.

AU - Garcia-Carbonero, R.

AU - Massuti, B.

AU - Queralt, C.

AU - Botia, M.

AU - Garcia-Gomez, R.

AU - Isla, D.

AU - Cobo, M.

AU - Santarpia, M.

AU - Cecere, F.

AU - Mendez, P.

AU - Sanchez, J. J.

AU - Rosell, R.

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N2 - Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/ gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

AB - Background: Impaired DNA repair capacity may favorably affect survival in cisplatin/gemcitabine-treated non-small-cell lung cancer (NSCLC) patients. We investigated the association of survival with genetic polymorphisms in X-ray repair cross-complementing group 1 and group 3 (XRCC3), xeroderma pigmentosum group D (XPD), excision repair cross-complementing group 1, ligase IV, ribonucleotide reductase, TP53, cyclooxygenase-2, interleukin-6, peroxisome proliferator-activated receptor γ, epidermal growth factor, methylene-tetra-hydrofolate reductase and methionine synthase. Patients and methods: One hundred and thirty-five stage IV or IIIB (with malignant pleural effusion) NSCLC patients treated with cisplatin/ gemcitabine from different hospitals of the Spanish Lung Cancer Group were genotyped for 14 different polymorphisms in 13 genes. Polymorphisms were detected by the TaqMan method, using genomic DNA extracted from baseline blood samples. Results: Median survival was significantly increased in patients harboring XRCC3 241 MetMet: 16 months versus 10 months for patients with ThrMet and 14 months for those with ThrThr (P = 0.01). The risk of death ratio was significantly lower for MetMet than for ThrMet patients (hazard ratio, 0.43; P = 0.01). In the multivariate Cox model, XRCC3 241 remained an independent prognostic factor (hazard ratio: XRCC3 241 MetMet, 0.44; P = 0.01), and XPD 751 and XRCC1 399 also emerged as significant prognostic factors (hazard ratios: XPD 751 LysGln, 0.46, = 0.03; XRCC1 399 ArgGln, 0.61, P = 0.04). No other association was observed between genotype and survival. Conclusion: XRCC3 241 MetMet is an independent determinant of favorable survival in NSCLC patients treated with cisplatin/gemcitabine. A simple molecular assay to determine the XRCC3 241 genotype can be useful for customizing chemotherapy.

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KW - DNA repair genes

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