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

Peñas, R. de las; Sanchez-Ronco, María; Alberola, Vicente; Tarón, Miquel; Camps, Carlos; Garcia-Carbonero, Rocío; Massutí, Bartomeu; Queralt, Cristina; Botia, Mónica; García-Gómez, Ramón; Isla, Dolores; Cobo, Manuel; Santarpía, Mariacarmela; Cecere, Fabiana Letizia; Méndez, Pedro Rafael Casado; Sánchez, José Javier; Rosell, Rafael

doi:10.1093/annonc/mdj135

Cited by 155 publications

(117 citation statements)

References 23 publications

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“…18 Additionally, reports in colorectal cancer patients show an improved survival for patients with XRCC1-399 G allele receiving 5-FU/oxaplatin chemotherapy. 19 Similar results were demonstrated in lung cancer, 20 breast cancer 21 and esophageal cancer. 22 Only one recent study has been published, supporting the pharmacogenetic role of XRCC1-399 polymorphism in gastric cancer patients.…”

Section: Discussionsupporting

confidence: 77%

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

et al. 2007

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Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Platinum agents have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in xeroderma pigmentosum group D (XPD), X-ray repair cross complementing group 1 (XRCC1) and glutathione S-transferase P1 (GSTP1) predicted overall survival in gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population. SNPs of XPD-751, XRCC1-399 and GSTP1-105 in 62 gastric cancer patients were evaluated using the TaqMan 5 0 nuclease assay. Genotypes were correlated to survival. The median overall survival time was 322 days (range: 56-2058 days). The median survival times for patients with Arg/Arg or Arg/Gln genotypes of XRCC1 gene were significantly longer than others (P ¼ 0.03). For 58 patients with ECOG PS (Eastern Cooperative Oncology Group performance status)r2, more obvious significance was demonstrated (P ¼ 0.002). Patients with XRCC1-399 Gln/Gln genotype demonstrated a significant worse survival. No significant association was found between SNPs of XPD-751, GSTP1-105 and survival (P ¼ 0.125, 0.475, respectively). XRCC1 genotyping might make tailor chemotherapy possible for gastric cancer patients treated with oxaliplatin-based chemotherapy.

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Section: Discussionsupporting

confidence: 77%

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

et al. 2007

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“…These results were in agreement with recent studies (de las Peñas et al, 2006;Tibaldi et al, 2008;Wang et al, 2010). Our data were also in accordance with a recent meta-analysis (Yin et al, 2011).…”

Section: Discussionsupporting

confidence: 94%

“…ERCC1 polymorphisms have been reported to predict better response Kalikaki et al, 2009;Li et al, 2010) or survival in NSCLC patients treated with platinum-based chemotherapy Ryu et al, 2004;Zhou et al, 2004). However, published reports of the associations between ERCC1 SNPs and clinical efficacy from individual studies are controversial (de las Peñas et al, 2006;Tibaldi et al, 2008;Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Hong

Wang

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C677T excision repair cross-complementation group 1 (ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods: A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 C118T were genotyped using the TaqMan methods. Results: The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype (TT or CT) (41.2% versus 19.1%, P=0.01). Median time to progression (TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype (7.6 months versus 5.0 months, P=0.003). No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions: Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

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“…Due to the comparative therapeutic advantage, cisplatin-based combination regimens are recommended as the optimal choice currently for the majority of NSCLC patients indicative of chemotherapy or adjuvant chemotherapy (2). However, the average survival time for patients with advanced stage of NSCLC receiving cisplatin plus gemcitabine treatment is ~16 months and may even be reduced to 12 months in those with cisplatin-resistance (3). The dilemma in managing late-stage NSCLC requires the elucidation of the mechanisms in cisplatin resistance to define novel, effective and applicable therapeutic targets for lung cancer (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…However, the average survival time for patients with advanced stage of NSCLC receiving cisplatin plus gemcitabine treatment is ~16 months and may even be reduced to 12 months in those with cisplatin-resistance (3). The dilemma in managing late-stage NSCLC requires the elucidation of the mechanisms in cisplatin resistance to define novel, effective and applicable therapeutic targets for lung cancer (2,3).…”

Section: Introductionmentioning

confidence: 99%

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

Wang

et al. 2014

Oncology Reports

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Abstract. Previous studies have shown that is inactivated in lung cancer cells, while the inactivation of the Wnt/β-catenin signaling pathway by Dkk3 inhibits lung cancer progression. In the present study, we investigated whether Dkk3 enhances the sensitivity of lung cancer cells to cisplatin. A549, Calu1 and H460 lung adenocarcinoma cell lines were transfected with DKK3 siRNA, while the cisplatin-resistant subline A549cis was transfected with DKK3. DKK3 expression was attenuated in A549cis, Calu1cis and H460cis compared to A549, Calu1 and H460, respectively. Lung adenocarcinoma cell growth, proliferation, apoptosis, cell cycle in vitro and in vivo were then analyzed. DKK3 knockdown by siRNA transfection rendered A549, Calu1 and H460 resistant to cisplatin. As a result of DKK3 transfection, the expression of DKK3 and E-cadherin was significantly upregulated, while that of MMP7, survivin, c-myc and cyclin D1 was downregulated. DKK3 overexpression retarded cell proliferation, induced cell cycle arrest and apoptosis, and reduced cell invasive ability in the A549 and A549cis cells. In addition, the proportions of apoptotic cells and the PARP level were significantly increased in A549cis-and H460cis-DKK3 cells treated with cisplatin. Moreover, tumor growth was retarded more in cisplatin-treated nude mice seeded with A549cis-DKK3 cells than with A549cis cells. Cell viability increased with the pretreatment of SB216763 for 2 h in A549cis and A549cis-DKK3 cells incubated with cisplatin (1 µM) for 72 h. In conclusion, the re-activation of Dkk3 enhances the chemosensitivity to cisplatin in cisplatin-resistant lung adenocarcinoma cell lines, which requires additional studies to realize this potential in clinical use. IntroductionLung cancer has emerged as the third leading cause of cancer-related mortality worldwide (1). In the USA, over 200,000 new lung cancer cases are diagnosed annually, causing over 150,000 deaths in one year (1). Approximately 85% of lung cancer patients suffer from non-small cell lung cancer (NSCLC). Due to the comparative therapeutic advantage, cisplatin-based combination regimens are recommended as the optimal choice currently for the majority of NSCLC patients indicative of chemotherapy or adjuvant chemotherapy (2). However, the average survival time for patients with advanced stage of NSCLC receiving cisplatin plus gemcitabine treatment is ~16 months and may even be reduced to 12 months in those with cisplatin-resistance (3). The dilemma in managing late-stage NSCLC requires the elucidation of the mechanisms in cisplatin resistance to define novel, effective and applicable therapeutic targets for lung cancer (2,3).Several signal transduction pathways controlling chemosensitivity are aberrantly activated in various types of cancer, among which Wnt is of special significance (4). The role of Wnt1/Int-1 in the induction of mouse mammary tumor as an integration site for mouse mammary tumor virus (MMTV) was first recognized 30 years ago (4). Wnt/β-catenin signaling is initiated by the binding of secre...

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

Abstract: 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.

Cited by 155 publications

References 23 publications

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma cells via the Wnt/β-catenin pathway

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