AIMS: Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. MATERIALS & METHODS: The study group comprised of 101 bladder cancer patients treated with platinum-based CRT, and seven polymorphisms in XPC (Lys939Gln, rs2228001), XPD (Lys751Gln, rs13181), XPG (Asp1104His, rs17655), XRCC1 (Arg399Gln, rs25487), XRCC3 (Thr241Met, rs861539), TP53 (Arg72Pro, rs1042522) and MDM2 (SNP309, T>G, rs2279744) were genotyped. RESULTS: More than two total variant alleles in nucleotide excision repair genes, including XPC, XPD and XPG, were significantly associated with grade 3 or 4 neutropenia (adjusted odds ratio [aOR]: 6.8; 95% CI: 2.0-26; p = 0.0026). There were no significant associations between any genotypes and grade 2 or greater nausea/vomiting or diarrhea. Any grade 3 or 4 hematological toxicity was significantly associated with the Gln/Gln or Lys/Gln + Gln/Gln genotypes of XPC compared with Lys/Lys (aOR: 10; 95% CI: 2.0-65; p = 0.0070 or aOR: 6.3; 95% CI: 1.9-29; p = 0.0069; respectively). CONCLUSION: These results suggest that nucleotide excision repair gene polymorphisms, especially in XPC, might potentially be predictive factors for acute toxicity of CRT for bladder cancer, helping individual patient selection for bladder conservation therapy. However, further studies with larger sample sizes are needed to draw final conclusions.
AIMS: Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, treatment-related toxicity remains a major consideration in therapeutic planning. Some common polymorphisms in genes involved in DNA repair (encoding enzymes that repair DNA damaged by platinum agents and ionizing radiation) are reported to result in modulation of the repair capacity. We investigated associations between functional genetic polymorphisms involved in DNA repair and acute toxicity of CRT to determine the predictive value of these polymorphisms for toxicity. MATERIALS & METHODS: The study group comprised of 101 bladder cancerpatients treated with platinum-based CRT, and seven polymorphisms in XPC (Lys939Gln, rs2228001), XPD (Lys751Gln, rs13181), XPG (Asp1104His, rs17655), XRCC1 (Arg399Gln, rs25487), XRCC3 (Thr241Met, rs861539), TP53 (Arg72Pro, rs1042522) and MDM2 (SNP309, T>G, rs2279744) were genotyped. RESULTS: More than two total variant alleles in nucleotide excision repair genes, including XPC, XPD and XPG, were significantly associated with grade 3 or 4 neutropenia (adjusted odds ratio [aOR]: 6.8; 95% CI: 2.0-26; p = 0.0026). There were no significant associations between any genotypes and grade 2 or greater nausea/vomiting or diarrhea. Any grade 3 or 4 hematological toxicity was significantly associated with the Gln/Gln or Lys/Gln + Gln/Gln genotypes of XPC compared with Lys/Lys (aOR: 10; 95% CI: 2.0-65; p = 0.0070 or aOR: 6.3; 95% CI: 1.9-29; p = 0.0069; respectively). CONCLUSION: These results suggest that nucleotide excision repair gene polymorphisms, especially in XPC, might potentially be predictive factors for acute toxicity of CRT for bladder cancer, helping individual patient selection for bladder conservation therapy. However, further studies with larger sample sizes are needed to draw final conclusions.
Authors: Most Umme Bushra; Sanzana Fareen Rivu; Ali Ehsan Sifat; Noor Ahmed Nahid; Maizbha Uddin Ahmed; Mir Md Abdullah Al-Mamun; Mohd Nazmul Hasan Apu; Md Siddiqul Islam; Md Reazul Islam; Mohammad Safiqul Islam; Abul Hasnat Journal: Mol Biol Rep Date: 2020-09-03 Impact factor: 2.316
Authors: Carlotta Sacerdote; Simonetta Guarrera; Fulvio Ricceri; Barbara Pardini; Silvia Polidoro; Alessandra Allione; Rossana Critelli; Alessia Russo; Angeline S Andrew; Yuanqing Ye; Xifeng Wu; Lambertus A Kiemeney; Andrea Bosio; Giovanni Casetta; Giuseppina Cucchiarale; Paolo Destefanis; Paolo Gontero; Luigi Rolle; Andrea Zitella; Dario Fontana; Paolo Vineis; Giuseppe Matullo Journal: Int J Cancer Date: 2013-04-25 Impact factor: 7.396
Authors: Elizabeth Smyth; Shenli Zhang; David Cunningham; Andrew Wotherspoon; Richie Soong; Clare Peckitt; Nicola Valeri; Matteo Fassan; Massimo Rugge; Alicia Okines; William Allum; Sally Stenning; Matthew Nankivell; Ruth Langley; Patrick Tan Journal: Clin Cancer Res Date: 2017-10-02 Impact factor: 12.531