Abstract
PurposeA two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT.Materials and methodsThe analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site.ResultsWe found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48–2.41; ppooled = 4.34 × 10−16).ConclusionThis first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted.
Highlights
Head and neck cancers (HNC) represent a group of patients with increasing loco-regional control and survival rates [1,2,3]
Increasing evidence points to an individual inherent predisposition of developing toxicity [5] and in 2009, the Radiogenomics Consortium [6, 7] was established, facilitating research efforts in genetic variations associated with RT-induced toxicity
Breast, prostate, gynaecological and lung cancer cohorts are represented in hypothesis-driven studies of associations between SNPs and RT-induced toxicity
Summary
Head and neck cancers (HNC) represent a group of patients with increasing loco-regional control and survival rates [1,2,3]. In studies of breast-, head and neck and prostate cancer cohorts, several SNPs associated with different morbidities after RT have been identified [8,9,10,11]. Two recent GWA studies explored RT-induced toxicity (temporal lobe brain injury and oral mucositis, respectively) in nasopharyngeal HNC patients [12, 13]. Another recent study of 37 patients identified associations between somatic genetic variants in HNC tumour tissue and severity of RT-induced morbidity, which is the first study to link genetic
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