title: Potential Role of Single Nucleotide Polymorphisms of XRCC1, XRCC3, and RAD51 in Predicting Acute Toxicity in Rectal Cancer Patients Treated With Preoperative Radiochemotherapy.
abstract: OBJECTIVE
  To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy.
  
  
  METHODS
  Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology.
  
  
  RESULTS
  The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group.
  
  
  CONCLUSIONS
  Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.
authors: Institute of Radiation Oncology.
authors: Mattia F
authors: MF
authors: Osti
authors: Institute of Radiation Oncology.
authors: Luca
authors: L
authors: Nicosia
authors: Institute of Radiation Oncology.
authors: Linda
authors: L
authors: Agolli
authors: Department of Advanced Molecular Diagnostic, Sapienza University.
authors: Giovanna
authors: G
authors: Gentile
authors: Institute of Radiation Oncology.
authors: Teresa
authors: T
authors: Falco
authors: Institute of Radiation Oncology.
authors: Stefano
authors: S
authors: Bracci
authors: Department of Public Health, Catholic University of Sacred Heart, Rome, Italy.
authors: Francesco
authors: F
authors: Di Nardo
authors: Institute of Radiation Oncology.
authors: Giuseppe
authors: G
authors: Minniti
authors: Institute of Radiation Oncology.
authors: Vitaliana
authors: V
authors: De Sanctis
authors: Institute of Radiation Oncology.
authors: Maurizio
authors: M
authors: Valeriani
authors: Institute of Radiation Oncology.
authors: Marianna
authors: M
authors: Maglio
authors: Department of Advanced Molecular Diagnostic, Sapienza University.
authors: Marina
authors: M
authors: Borro
authors: Department of Advanced Molecular Diagnostic, Sapienza University.
authors: Maurizio
authors: M
authors: Simmaco
authors: Institute of Radiation Oncology.
authors: Riccardo M
authors: RM
authors: Enrici
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069287:Capecitabine / Q000627:therapeutic use; D059248:Chemoradiotherapy / Q000009:adverse effects*; D003556:Cystitis / Q000209:etiology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003967:Diarrhea / Q000209:etiology / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017699:Pelvic Pain / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011349:Proctitis / Q000209:etiology / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics*; D011855:Radiodermatitis / Q000209:etiology / Q000235:genetics; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D000076105:X-ray Repair Cross Complementing Protein 1 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D000069287:Capecitabine; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D005472:Fluorouracil