title: Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: association with genetic polymorphism in DNA DSB repair genes.
abstract: OBJECTIVE
  The aim of this study was to investigate the association between polymorphic variants of DNA repair genes with the susceptibility of acute oral mucositis (OM) in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy.
  
  
  METHODS
  The study population consisted of 120 NPC patients treated with intensity-modulated radiation therapy (IMRT). Among them 70 patients also received concurrent chemotherapy. Genotypes in DNA repair genes Ku70 c.-1310C>G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099-2408G> A (rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase chain reaction combined with the restriction fragment length polymorphism (PCR-RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into the CTC0-2 group (CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using the multivariate logistic regression analysis.
  
  
  RESULTS
  A significant difference in Ku70 c.1781G> T genotype distribution was observed between the CTC0-2 and CTC3 + groups for the 120 patients analyzed. The GG carriers were at higher risks for severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287-6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80 (c.2099-2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development of severe oral mucositis. Stratification analyses for the 50 patients treated with radiation alone further confirmed the association between the variant genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183-22.238, p = 0.029). Concurrent radiochemotherapy increased the risk of severe OM for both the TT homozygotes and GG genotypes.
  
  
  CONCLUSIONS
  Our study suggests that the Ku70 c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral mucositis in Chinese nasopharyngeal carcinoma patients.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei , P. R. China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Ren
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Dai
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.forename: Cui-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Kun-Yu
authors.initials: KY
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: C-M Charlie
authors.initials: CM
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000378:metabolism; D002277:Carcinoma; D020134:Catalytic Domain; D002681:China; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D013280:Stomatitis / Q000473:pathology*; D055815:Young Adult
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen