Nucleotide Excision Repair Gene Polymorphisms May Predict Acute Toxicity in Patients Treated with Chemoradiotherapy for Bladder Cancer

Sakano, Shigeru; Hinoda, Yuji; Sasaki, Miwa; Wada, Takashi; Matsumoto, Hiroaki; Eguchi, Satoshi; Shinohara, Asano; Kawai, Yosuke; Hara, Tomohiko; Nagao, Kazuhiro; Hara, Takahiko; Naito, Katsusuke; Matsuyama, Hideyasu

doi:10.2217/pgs.10.106

Cited by 47 publications

(37 citation statements)

References 37 publications

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“…The patients received combined platinum-based systemic CRT. In the majority of patients, one cycle of the regimen (based on Shipley's method with slight modification) (17) included administration of cisplatin (70 mg̸m 2 ) on day 1, followed by radiation at 1.8 Gy per fraction on days 2-5 in the first week and every 5 days consecutively in the second week (18)(19)(20). Radiotherapy involved 10-MV photons with a 4-field technique, treating the bladder and pelvic lymph nodes to 32.4 Gy during 2 cycles, followed by a CT-planned whole-bladder boost of 16.2 Gy for an additional cycle.…”

Section: Methodsmentioning

confidence: 99%

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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Abstract. Combined trimodality therapy, including transurethral resection and platinum-based chemoradiotherapy, has shown promising results for muscle-invasive bladder cancer. However, this type of treatment may decrease survival as a result of delayed cystectomy in patients with non-responding tumors. DNA repair proteins may affect survival of bladder cancer patients receiving combined trimodality therapy, by affecting the perioperative nature of the tumor cells or by repairing DNA damaged by platinum agents and radiation. We investigated the associations of excision repair cross-complementing group 1 (ERCC1), X-ray repair cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with response and survival in 157 locally advanced bladder cancer patients receiving combined trimodality therapy, in order to determine the predictive value of the expression of these proteins in patient selection for therapy. We examined ERCC1, XRCC1 and APE1 expression in tumor specimens using immunohistochemistry. Patients positive for ERCC1, positive for XRCC1 and positive for either ERCC1 or XRCC1, exhibited significantly improved disease-specific survival rates (P=0.023, 0.025 and 0.0091, respectively). In multivariate analysis, combined ERCC1 and XRCC1 expression was independently associated with disease-specific mortality [risk ratio (RR): 0.64; 95% confidence interval (CI), 0.43-0.94 and P=0.024]. Thus, combined ERCC1 and XRCC1 expression may serve as an independent prognostic marker for survival in bladder cancer patients receiving combined trimodality therapy. Prospective studies with a larger sample size are required to confirm these results.

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Section: Methodsmentioning

confidence: 99%

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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“…[31][32][33] However, such studies using cell lines could not replicate the findings from population-based studies, which had reported significant associations between SNPs in multiple genes (eg, drug metabolism genes, DNA repair genes, and apoptosis genes) and the toxicity response. [34][35][36][37] This difference might have resulted from different mechanisms underlying the toxicity responses of the 2 levels (cell line and individual). The p53 pathway plays important roles in chemotherapy response and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

“…The association between the functional SNP T309G (rs2279744) and platinum-based or noneplatinum-based chemotherapy responses has been investigated in many cancers. 18,35,[40][41][42][43] However, the results have been inconsistent regarding the effects of this SNP on gastrointestinal and hematologic toxicities. No significant effects were found in 136 patients with bladder cancer who received combined cisplatinbased systemic chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…No significant effects were found in 136 patients with bladder cancer who received combined cisplatinbased systemic chemotherapy and radiotherapy. 35 One recent study observed a significant association between severe hematologic and overall toxicities and SNP309 in 444 patients with advanced NSCLC treated with platinum-based chemotherapy. 18 Although this SNP was not included in our study, one of its high LD SNP rs3730581 (pairwise LD r 2 ¼ 0.86), had been investigated but did not show a significant effect on any chemotherapy toxicity.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC

Qian

Liu

et al. 2015

Clinical Lung Cancer

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We investigated the association of 5 tagging single nucleotide polymorphisms (SNPs) of MDM2 with chemotherapy-related toxicities and clinical outcomes in 663 patients with advanced nonesmall-cell lung cancer. We identified 2 SNPs (rs1470383 and rs1690924) with significant associations with chemotherapyrelated toxicities. One SNP rs1470383 also influenced the overall survival of patients without overall toxicity or hematologic toxicity. Introduction: Platinum agents can cause the formation of DNA adducts and induce apoptosis to eliminate tumor cells. The aim of the present study was to investigate the influence of genetic variants of MDM2 on chemotherapy-related toxicities and clinical outcomes in patients with advanced nonesmall-cell lung cancer (NSCLC). Materials and Methods: We recruited 663 patients with advanced NSCLC who had been treated with first-line platinum-based chemotherapy. Five tagging single nucleotide polymorphisms (SNPs) in MDM2 were genotyped in these patients. The associations of these SNPs with clinical toxicities and outcomes were evaluated using logistic regression and Cox regression analyses. Results: Two SNPs (rs1470383 and rs1690924) showed significant associations with chemotherapy-related toxicities (ie, overall, hematologic, and gastrointestinal toxicity). Compared with the wild genotype AA carriers, patients with the GG genotype of rs1470383 had an increased risk of overall toxicity (odds ratio [OR], 3.28; 95% confidence interval [CI], 1.34-8.02; P ¼ .009) and hematologic toxicity (OR, 4.10; 95% CI, 1.73-9.71; P ¼ .001). Likewise, patients with the AG genotype of rs1690924 showed more sensitivity to gastrointestinal toxicity than did those with the wild-type homozygote GG (OR, 2.32; 95% CI, 1.30-4.14; P ¼ .004). Stratified survival analysis revealed significant associations between rs1470383 genotypes and overall survival in patients without overall or hematologic toxicity (P ¼ .007 and P ¼ .0009, respectively). Conclusion: The results of our study suggest that SNPs in MDM2 might be used to predict the toxicities of platinum-based chemotherapy and overall survival in patients with advanced NSCLC. Additional validations of the association are warranted.

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“…carriership of polymorphisms in the XPD, ERCC1 and XRCC1 genes conferring lower capacity for DnA repair has been shown to be associated with higher risk for acute and late toxicity in 'standard' chemotherapy or radiotherapy regimens (40,59). What is more, polymorphic variants of genes which are not known to be associated with substantial decrease in the capacity for DnA repair may apparently also modify the risk for toxicity following anticancer therapy, as the R allele of the P72R polymorphism has been found to be more frequent in vascular skin lesions following radiotherapy for breast cancer than the P allele (61).…”

Section: Using Information About Individual Repair Capacity For Desigmentioning

confidence: 99%

War without Weapons—Constitution of Healthy and Pathological Phenotypes Associated with Polymorphisms in Genes Involved in the Maintenance of Genome Integrity

Oluwaseun

Khalil

2012

Biotechnology & Biotechnological Equipment

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Nucleotide Excision Repair Gene Polymorphisms May Predict Acute Toxicity in Patients Treated with Chemoradiotherapy for Bladder Cancer

Cited by 47 publications

References 37 publications

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC

War without Weapons—Constitution of Healthy and Pathological Phenotypes Associated with Polymorphisms in Genes Involved in the Maintenance of Genome Integrity

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