Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy

Ruzzo, Annamaria; Graziano, Francesco; Kawakami, Kazuyuki; Watanabe, Go; Santini, Daniele; Catalano, Vincenzo; Bisonni, Renato; Canestrari, Emanuele; Ficarelli, R.; Menichetti, Ettore Tito; Mari, D.; Testa, E.; Silva, Rosarita; Vincenzi, Bruno; Giordani, Paolo; Cascinu, Stefano; Giustini, Lucio; Tonini, Giuseppe; Magnani, Mauro

doi:10.1200/jco.2005.04.8322

Cited by 121 publications

(108 citation statements)

References 45 publications

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“…We found that high DPD expression, high ERCC1 expression, and low EGFR expression in GC specimens were significant predictors of poor survival in advanced GC. Recently, several studies have reported that patients' genetic profiles are related to the outcomes of cancer therapy (van 't Veer et al, 2002;Ruzzo et al, 2006). In colorectal cancer, since many studies have examined molecular predictors of outcomes during the past decade, TS, DPD, and TP were newly included in 'ASCO 2006 tumour marker guidelines in gastrointestinal cancer' (Locker et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have reported that the MTHFR 677T mutation, linked to the reduced activity of MTHFR, increases chemosensitivity to 5-FU (Cohen et al, 2003;Sohn et al, 2004), whereas others have had inconsistent results (Etienne et al, 2004;Ruzzo et al, 2006). Although MTHFR and DHFR are key enzymes in folate metabolism, the role of MTHFR gene expression in the antitumour activity of 5-FU remains controversial.…”

Section: Discussionmentioning

confidence: 99%

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Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Matsubara¹,

Nishina

Yamada³

et al. 2008

Br J Cancer

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Using laser-captured microdissection and a real-time RT -PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair crosscomplementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P ¼ 0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P ¼ 0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55 -3.67)), high DPD (HR: 2.04 (1.37 -3.02)), low EGFR (HR: 0.34 (0.20 -0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001 -1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Matsubara¹,

Nishina

Yamada³

et al. 2008

Br J Cancer

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“…However, other studies on lung cancer [10] and colorectal cancer [9,11,20,21] showed opposite results. In addition, several studies demonstrated that no clear association was found between ERCC1 codon 118 polymorphism and platinum sensitivity [24][25][26] . In a recent study on advanced gastric cancer treated with fluorouracil/cisplatin palliative chemotherapy, a tendency to higher response rate was found in patients with C allele (P = 0.09).…”

Section: Discussionmentioning

confidence: 99%

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Huang¹,

Dong²,

Du³

et al. 2008

WJG

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in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy (P < 0.05).CONCLUSION: ERCC1 codon 118 polymorphism has no significant impact on ERCC1 mRNA expression, and the intratumoral ERCC1 mRNA level but not codon 118 polymorphism may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy. INTRODUCTIONIn China, gastric cancer is the leading cause of cancer deaths, accounting for nearly one-fourth of all cancer deaths. Surgery is the primary modality for managing early-stage and locally-advanced disease. However, even after gastrectomy, the majority of patients develop local or distant recurrence [1] . Adjuvant chemotherapy for gastric cancer has been under clinical investigation for more than four decades. Fluoropyrimidines, platinumdrugs and taxanes were shown to be effective in the treatment of gastric cancer. However, the response rates of these drugs or their combinations were less than 50% [2,3] . There is no standard regimen for postoperative treatment at the moment. Having an effective assay to predict the response to a given chemotherapeutic protocol beforehand would greatly enhance the success rate as well as the life quality of the patients.The nucleotide excision repair (NER) system plays a significant role in repairing a variety of distorting Abstract AIM: To determine the influence of excision repair cross complementing group 1 (ERCC1 ) codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS: Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS: No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 mo, respectively. The relapse-free and overall survivals in patients with low levels of ERCC1 mRNA were significantly longer than those in patients with high levels (P < 0.05), while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival

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“…The influence of NER and GST polymorphisms are well described in solid and hematological malignancies. 5,9,[18][19][20][21] Increased lung relapse and improved overall survival in GSTM1 null and GSTT1 null patients, respectively, was recently reported in 80 osteosarcoma patients. 22 A further small study reported an association between excision repair cross-complementation group 2 (ERCC2) c.2251A>C p.Lys 751 Gln, poor histological response, and inferior survival.…”

Section: Introductionmentioning

confidence: 99%

Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma

Windsor

Strauss

Kallis

et al. 2011

Cancer

122

144

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BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young people. Efficacy of multiagent MAP (methotrexate, doxorubicin [Adriamycin], cisplatin) chemotherapy may be influenced by multiple cellular pathways. This pilot study aimed to investigate the association of 36 candidate genetic polymorphisms in MAP pathway genes with histological response, survival, and grade 3‐4 chemotherapy toxicity in osteosarcoma. METHODS: Blood samples were obtained from 60 patients who had completed MAP chemotherapy. All patients were manually genotyped for 5 polymorphisms. The remaining 31 polymorphisms were genotyped in 50 patients using the Illumina 610‐Quad microarray. Associations between candidate polymorphisms and histological response, progression‐free survival, and toxicity were estimated using Pearson chi‐square and Fisher exact tests, the Kaplan‐Meier method, the log‐rank test, and the Cox proportional hazards model. RESULTS: Poor histological response was increased in variants of ABCC2 c.24C>T (P = .011) and GSTP1 c.313A>G p.Ile105Val (P = .009), whereas MTHFD1 c.1958G>A p.Arg653Gln was protective (P = .03). Methotrexate toxicity was increased in variants of MTHFR c.1298A>C p.Glu429Ala (P = .038), ABCB1 c.3435T>C Ile145Ile (P = .027), and ABCC2 c.3563T>A p.Val1188Glu (P = .028). Variants of GSTP1 c.313A>G p.Ile105Val were at increased risk of myelosuppression (P = .024) and cardiac damage (P = .008). CONCLUSIONS: This pilot study represents the most comprehensive study to date examining the role of genetic polymorphisms in osteosarcoma. Although small and retrospective, it shows that several polymorphisms appear to significantly influence toxicity and clinical outcome. These deserve prospective validation in the hope of optimizing treatment for resistant disease and reducing the late effects burden. Cancer 2012. © 2011 American Cancer Society.

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Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy

Abstract: Specific polymorphisms may influence clinical outcomes of AGC patients. Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospective studies.

Cited by 121 publications

References 45 publications

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma

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