title: Osteoradionecrosis in head-and-neck cancer has a distinct genotype-dependent cause.
abstract: OBJECTIVE
  We performed a case-control study to establish whether the development of osteoradionecrosis (ORN) was related to a variant allele substituting T for C at -509 of the transforming growth factor-β1 gene (TGF-β1).
  
  
  METHODS
  A total of 140 patients, 39 with and 101 without ORN, who underwent radiotherapy for head-and-neck cancer with a minimum of 2 years follow-up, were studied. None of the patients had clinical evidence of recurrence at this time. DNA extracted from blood was genotyped for the -509 C-T variant allele of the TGF-β1 gene.
  
  
  RESULTS
  There were no significant differences in patient, cancer treatment, or tumor characteristics between the two groups. Of the 39 patients who developed ORN, 9 were homozygous for the common CC allele, 19 were heterozygous, and 11 were homozygous for the rare TT genotype. Of the 101 patients without ORN, the distribution was 56 (CC), 33 (CT), and 12 (TT). The difference in distribution was significant, giving an increased risk of ORN of 5.7 (95% CI, 1.7-19.2) for homozygote TT patients (p = 0.001) and 3.6 (95% CI, 1.3-10.0) for heterozygotes (p = 0.004) when compared with patients with the CC genotype. Postradiotherapy dentoalveolar surgery preceding the development of ORN was associated with the CC genotype (p = 0.02).
  
  
  CONCLUSIONS
  Our findings support the postulate that the development of ORN is related to the presence of the T variant allele at -509 within the TGF-β1 gene.
authors.affiliation: Head and Neck Unit, Guy's and St. Thomas' Hospital NHS Foundation Trust, London, UK. Andrew.Lyons@gstt.nhs.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lyons
authors.forename: Catharine M
authors.initials: CM
authors.lastname: West
authors.forename: Janet M
authors.initials: JM
authors.lastname: Risk
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Slevin
authors.forename: Clara
authors.initials: C
authors.lastname: Chan
authors.forename: Siobhan
authors.initials: S
authors.lastname: Crichton
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rinck
authors.forename: Dawn
authors.initials: D
authors.lastname: Howell
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010025:Osteoradionecrosis / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1