A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer

Abstract Background Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort....

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Autores principales:	Elnaz Naderi, Anne Petra Gerarda Crijns, Roel Johannes Henricus Marinus Steenbakkers, Johanna Geertruida Maria van den Hoek, Hendrika Marike Boezen, Behrooz Ziad Alizadeh, Johannes Albertus Langendijk
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Radiogenomics GWAS Radiation-induced toxicity Head and neck cancer Medicine R
Acceso en línea:	https://doaj.org/article/d2b527daec7c40419e2912e942d7b6cd
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spelling	oai:doaj.org-article:d2b527daec7c40419e2912e942d7b6cd2021-11-28T12:06:41ZA two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer10.1186/s12967-021-03145-11479-5876https://doaj.org/article/d2b527daec7c40419e2912e942d7b6cd2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03145-1https://doaj.org/toc/1479-5876Abstract Background Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort. Methods A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed. Results A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10–8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value < = 3.78 × 10–9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10–5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05). Conclusions This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.Elnaz NaderiAnne Petra Gerarda CrijnsRoel Johannes Henricus Marinus SteenbakkersJohanna Geertruida Maria van den HoekHendrika Marike BoezenBehrooz Ziad AlizadehJohannes Albertus LangendijkBMCarticleRadiogenomicsGWASRadiation-induced toxicityHead and neck cancerMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Radiogenomics GWAS Radiation-induced toxicity Head and neck cancer Medicine R
spellingShingle	Radiogenomics GWAS Radiation-induced toxicity Head and neck cancer Medicine R Elnaz Naderi Anne Petra Gerarda Crijns Roel Johannes Henricus Marinus Steenbakkers Johanna Geertruida Maria van den Hoek Hendrika Marike Boezen Behrooz Ziad Alizadeh Johannes Albertus Langendijk A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
description	Abstract Background Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort. Methods A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed. Results A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value < 5.0 × 10–8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value < = 3.78 × 10–9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value < 1.0 × 10–5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value < 0.05). Conclusions This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.
format	article
author	Elnaz Naderi Anne Petra Gerarda Crijns Roel Johannes Henricus Marinus Steenbakkers Johanna Geertruida Maria van den Hoek Hendrika Marike Boezen Behrooz Ziad Alizadeh Johannes Albertus Langendijk
author_facet	Elnaz Naderi Anne Petra Gerarda Crijns Roel Johannes Henricus Marinus Steenbakkers Johanna Geertruida Maria van den Hoek Hendrika Marike Boezen Behrooz Ziad Alizadeh Johannes Albertus Langendijk
author_sort	Elnaz Naderi
title	A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
title_short	A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
title_full	A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
title_fullStr	A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
title_full_unstemmed	A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
title_sort	two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/d2b527daec7c40419e2912e942d7b6cd
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A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer

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