XRCC1 (rs25487) polymorphism is associated with severe oral mucositis and poor treatment response after radiotherapy for oropharyngeal carcinoma

Abstract

To investigate the association of Single Nucleotide Polymorphisms of DNA repair genes and patient-specific clinical characteristics with the risk of developing severe acute radiotoxicities and treatment response in Oropharyngeal Carcinoma. 179 cases of Oropharyngeal Carcinoma treated with 2-D radical radiotherapy were evaluated for acute radiotoxicity end-points viz; oral mucositis, dermatitis, dysphagia, and xerostomia; and the resultant requirement of nasogastric feeding tube, significant (>\u200910%) weight loss during treatment and treatment break(s). Eleven Single Nucleotide Polymorphisms of DNA repair genes were analyzed using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and correlated with the severity of these radiotoxicities (Common Toxicity Criteria for Adverse Events v4.0 grading) and the treatment response. Clinical parameters like age, Karnofsky Performance Status, smoking and tobacco chewing, etc. were also analysed in relation to the above. Homozygous AA genotype of XRCC1 (rs25487) (p\u2009=\u20090.024*, OR 2.629, 95% CI 1.136–6.087), Karnofsky Performance Status\u2009<\u200980 (p\u2009=\u20090.050*, OR 2.723, CI 1.000–7.418) and history of tobacco chewing (p\u2009=\u20090.030*, OR 2.615, 95% CI 1.099–6.222) were independent predictive factors for increased risk of severe (≥\u2009grade 3) mucositis. Also, the presence of Homozygous AA genotype of XRCC1(rs25487) was significantly associated with poor response to radiotherapy in these patients (p\u2009=\u20090.014, OR 2.235, 95% CI 1.074–5.744). Our findings illustrate that patients with Homozygous AA genotype of XRCC1 (rs25487) and certain clinical characteristics are likely to develop severe acute mucositis after radiotherapy for Oropharyngeal Carcinoma and the presence of this polymorphism is also associated with poor response to treatment.