Objective: The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy.
Methods: The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose.
Results: A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia.
Conclusions: To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.
Keywords: XRCC3; intensity modulation radiated therapy; nasopharyngeal carcinoma; radiation-induced xerostomia; single-nucleotide polymorphism.