Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis
Abstract Background Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associate...
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2020-06-01
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Online Access: | http://link.springer.com/article/10.1186/s12967-020-02390-0 |
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doaj-418cd6bdb79d47f684fae94457831aac |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Da-Wei Yang Tong-Min Wang Jiang-Bo Zhang Xi-Zhao Li Yong-Qiao He Ruowen Xiao Wen-Qiong Xue Xiao-Hui Zheng Pei-Fen Zhang Shao-Dan Zhang Ye-Zhu Hu Guo-Ping Shen Mingyuan Chen Ying Sun Wei-Hua Jia |
spellingShingle |
Da-Wei Yang Tong-Min Wang Jiang-Bo Zhang Xi-Zhao Li Yong-Qiao He Ruowen Xiao Wen-Qiong Xue Xiao-Hui Zheng Pei-Fen Zhang Shao-Dan Zhang Ye-Zhu Hu Guo-Ping Shen Mingyuan Chen Ying Sun Wei-Hua Jia Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis Journal of Translational Medicine Radiation injuries Oral mucositis Radiogenomics Genome-wide association study Functional mapping |
author_facet |
Da-Wei Yang Tong-Min Wang Jiang-Bo Zhang Xi-Zhao Li Yong-Qiao He Ruowen Xiao Wen-Qiong Xue Xiao-Hui Zheng Pei-Fen Zhang Shao-Dan Zhang Ye-Zhu Hu Guo-Ping Shen Mingyuan Chen Ying Sun Wei-Hua Jia |
author_sort |
Da-Wei Yang |
title |
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
title_short |
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
title_full |
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
title_fullStr |
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
title_full_unstemmed |
Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
title_sort |
genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2020-06-01 |
description |
Abstract Background Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy. Methods A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes. Results We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10–6.57; P = 6.33 × 10−6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10−7). Conclusions These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications. |
topic |
Radiation injuries Oral mucositis Radiogenomics Genome-wide association study Functional mapping |
url |
http://link.springer.com/article/10.1186/s12967-020-02390-0 |
work_keys_str_mv |
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doaj-418cd6bdb79d47f684fae94457831aac2020-11-25T03:34:40ZengBMCJournal of Translational Medicine1479-58762020-06-0118111210.1186/s12967-020-02390-0Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositisDa-Wei Yang0Tong-Min Wang1Jiang-Bo Zhang2Xi-Zhao Li3Yong-Qiao He4Ruowen Xiao5Wen-Qiong Xue6Xiao-Hui Zheng7Pei-Fen Zhang8Shao-Dan Zhang9Ye-Zhu Hu10Guo-Ping Shen11Mingyuan Chen12Ying Sun13Wei-Hua Jia14State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterDepartment of Radiation Oncology, Sun Yat-sen University First Affiliated HospitalState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer CenterAbstract Background Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy. Methods A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes. Results We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10–6.57; P = 6.33 × 10−6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10−7). Conclusions These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.http://link.springer.com/article/10.1186/s12967-020-02390-0Radiation injuriesOral mucositisRadiogenomicsGenome-wide association studyFunctional mapping |