title: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers.
abstract: BACKGROUND
  Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.
  
  
  METHODS
  A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).
  
  
  RESULTS
  Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.
  
  
  CONCLUSIONS
  Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.
authors.affiliation: Radiation Biology Section, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. galsbeih@kfshrc.edu.sa
authors.forename: Ghazi
authors.initials: G
authors.lastname: Alsbeih
authors.forename: Medhat
authors.initials: M
authors.lastname: El-Sebaie
authors.forename: Najla
authors.initials: N
authors.lastname: Al-Harbi
authors.forename: Khaled
authors.initials: K
authors.lastname: Al-Hadyan
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shoukri
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Rajhi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000532:radiotherapy*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011832:Radiation Injuries / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor