Universität zu Köln

Brooker, Rachel C., Antczak, Philipp, Liloglou, Triantafillos, Risk, Janet M., Sacco, Joseph J., Schache, Andrew G. and Shaw, Richard J. (2021). Genetic variants associated with mandibular osteoradionecrosis following radiotherapy for head and neck malignancy. Radiother. Oncol., 165. S. 87 - 94. CLARE: ELSEVIER IRELAND LTD. ISSN 1879-0887

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Abstract

Background/Aim: Utilising radiotherapy in the management of head and neck cancer (HNC) often results in long term toxicities. Mandibular osteoradionecrosis (ORN) represents a late toxicity associated with significant morbidity. We aim to identify a panel of common genetic variants which can predict ORN to aid development of personalised radiotherapy protocols. Method: Single nucleotide polymorphism (SNP) arrays were applied to DNA samples from patients who had prior HNC radiotherapy and minimum two years follow-up. A case cohort of mandibular ORN was compared to a control group of participants recruited to CRUK HOPON clinical trial. Relevant clinical parameters influencing ORN risk (e.g. smoking/alcohol) were collected. Significant associations from array data were internally validated using polymerase chain reaction (PCR) and pyrosequencing. Results: Following inclusion of 141 patients in the analysis (52 cases, 89 controls), a model predictive for ORN was developed; after controlling for alcohol consumption, smoking, and age, 4053 SNPs were identified as significant. This was reduced to a representative model of 18 SNPs achieving 92% accuracy. Following internal technical validation, a six SNP model (rs34798038, rs6011731, rs2348569, rs530752, rs7477958, rs1415848) was retained within multivariate regression analysis (ROC AUC 0.859). Of these, four SNPs (rs34798038 (A/G) (p 0.006), rs6011731 (C/T) (p 0.018), rs530752 (A/G) (p 0.046) and rs2348569 (G/G) (p 0.005)) were significantly associated with the absence of ORN. Conclusion: This is the first genome wide association study in HNC using ORN as the endpoint and offers new insight into ORN pathogenesis. Subject to validation, these variants may guide patient selection for personalised radiotherapy strategies. (c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 165 (2021) 87-93

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brooker, Rachel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Antczak, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Liloglou, Triantafillos UNSPECIFIED UNSPECIFIED UNSPECIFIED Risk, Janet M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sacco, Joseph J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schache, Andrew G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shaw, Richard J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-578946
DOI:	10.1016/j.radonc.2021.10.020
Journal or Publication Title:	Radiother. Oncol.
Volume:	165
Page Range:	S. 87 - 94
Date:	2021
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1879-0887
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FUNCTIONAL ANNOTATION; RISK-FACTORS; CANCER; MANAGEMENT; SNPNEXUS; DATABASE; JAW Multiple languages Oncology; Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57894