Osteoradionecrosis in Head-and-Neck Cancer Has a Distinct Genotype-Dependent Cause

• Published in: International journal of radiation oncology, biology, physics Vol. 82; no. 4; pp. 1479 - 1484
• Main Authors: Lyons, Andrew J., M.S., F.R.C.S, West, Catharine M., Ph.D, Risk, Janet M., Ph.D, Slevin, Nick J., F.R.C.R, Chan, Clara, F.R.C.R, Crichton, Siobhan, M.Sc, Rinck, Gabrielle, Ph.D, Howell, Dawn, B.Sc, Shaw, Richard J., M.D., F.D.S., F.R.C.S
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.03.2012; Elsevier
• Subjects: Adult; Aged; Alleles; Biological and medical sciences; BLOOD; Case-Control Studies; Diseases of the osteoarticular system; DNA; Female; GENES; GENOTYPE; GROWTH FACTORS; HAZARDS; HEAD; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; Head-and-neck cancer; Hematology, Oncology and Palliative Medicine; Humans; Male; Medical sciences; Middle Aged; NECK; NEOPLASMS; OSTEORADIONECROSIS; Osteoradionecrosis - genetics; Osteoradionecrosis - metabolism; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; PATIENTS; Post-radiotherapy; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Retrospective Studies; SURGERY; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-β1; Tumors; Variant allele; Vascular bone diseases; Post-radiotherapy; Head-and-neck cancer; Genotype; Transforming growth factor-β1; Variant allele; Osteoradionecrosis; Genetic variability; Diseases of the osteoarticular system; Osteonecrosis; Malignant tumor; Radiotherapy; Variant; Allele; Cancerology; Treatment; ENT disease; Head and neck cancer; Genetics; Transforming growth factor β1; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.05.016

Purpose 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). Patients and 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.