Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context
Summary: Background: The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423001536 |
| _version_ | 1797833152521043968 |
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| author | Qiao-Ling Wang Tong-Min Wang Chang-Mi Deng Wen-Li Zhang Yong-Qiao He Wen-Qiong Xue Ying Liao Da-Wei Yang Mei-Qi Zheng Wei-Hua Jia |
| author_facet | Qiao-Ling Wang Tong-Min Wang Chang-Mi Deng Wen-Li Zhang Yong-Qiao He Wen-Qiong Xue Ying Liao Da-Wei Yang Mei-Qi Zheng Wei-Hua Jia |
| author_sort | Qiao-Ling Wang |
| collection | DOAJ |
| description | Summary: Background: The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development. Methods: A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank. Findings: We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero = 0.94, 95% CI = 0.90–0.97, P = 1.29 × 10−4) and head and neck cancer (ORhetero = 0.91, 95% CI = 0.86–0.96, P = 1.56 × 10−3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero = 0.92, 95% CI = 0.87–0.98, P = 8.38 × 10−3) and class II locus (ORhetero = 0.89, 95% CI = 0.86–0.92, P = 1.65 × 10−10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero = 0.85, 95% CI = 0.75–0.96, P = 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P = 9.39 × 10−3) and diffuse large B cell lymphoma (Pclass I = 4.12 × 10−4; Pclass Ⅱ = 4.71 × 10−5), as well as the smoking subgroups of lung cancer (P = 7.45 × 10−5) and head and neck cancer (P = 4.55 × 10−3). Interpretation: We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development. Funding: This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708). |
| first_indexed | 2024-04-09T14:18:50Z |
| format | Article |
| id | doaj.art-c3f1f664b97b43e3bac1b1ce4b6c173f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-09T14:18:50Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c3f1f664b97b43e3bac1b1ce4b6c173f2023-05-05T04:40:51ZengElsevierEBioMedicine2352-39642023-06-0192104588Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in contextQiao-Ling Wang0Tong-Min Wang1Chang-Mi Deng2Wen-Li Zhang3Yong-Qiao He4Wen-Qiong Xue5Ying Liao6Da-Wei Yang7Mei-Qi Zheng8Wei-Hua Jia9State 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 Center, Guangzhou, China; School of Public Health, Sun Yat-sen University, Guangzhou, ChinaState 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 Center, Guangzhou, China; Corresponding author. State 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 Center, 651 Dongfeng East Road, Guangzhou, China.State 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, China; School of Public Health, Sun Yat-sen University, Guangzhou, ChinaState 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 Center, Guangzhou, ChinaState 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 Center, Guangzhou, China; School of Public Health, Sun Yat-sen University, Guangzhou, China; Corresponding author. State 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 Center, 651 Dongfeng East Road, Guangzhou, China.Summary: Background: The human leukocyte antigen (HLA) is a highly polymorphic region, and HLA diversity may play a role in presenting tumour-associated peptides and inducing immune responses. However, the effect of HLA diversity on cancers has not been fully assessed. We aimed to explore the role of HLA diversity on cancer development. Methods: A pan-cancer analysis was performed to evaluate the effect of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence (HED), on the susceptibility of 25 cancers in the UK Biobank. Findings: We observed that the diversity of HLA class II locus was associated with a lower risk of lung cancer (ORhetero = 0.94, 95% CI = 0.90–0.97, P = 1.29 × 10−4) and head and neck cancer (ORhetero = 0.91, 95% CI = 0.86–0.96, P = 1.56 × 10−3). Besides, a lower risk of non-Hodgkin lymphoma was associated with an increased diversity of HLA class I (ORhetero = 0.92, 95% CI = 0.87–0.98, P = 8.38 × 10−3) and class II locus (ORhetero = 0.89, 95% CI = 0.86–0.92, P = 1.65 × 10−10). A lower risk of Hodgkin lymphoma was associated with the HLA class I diversity (ORhetero = 0.85, 95% CI = 0.75–0.96, P = 0.011). The protective effect of HLA diversity was mainly observed in pathological subtypes with higher tumour mutation burden, such as lung squamous cell carcinoma (P = 9.39 × 10−3) and diffuse large B cell lymphoma (Pclass I = 4.12 × 10−4; Pclass Ⅱ = 4.71 × 10−5), as well as the smoking subgroups of lung cancer (P = 7.45 × 10−5) and head and neck cancer (P = 4.55 × 10−3). Interpretation: We provided a systematic insight into the effect of HLA diversity on cancers, which might help to understand the etiological role of HLA on cancer development. Funding: This study was supported by grants from the National Natural Science Foundation of China (82273705, 82003520); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the Science and Technology Planning Project of Guangzhou, China (201804020094); Sino-Sweden Joint Research Programme (81861138006); the National Natural Science Foundation of China (81973131, 81903395, 81803319, 81802708).http://www.sciencedirect.com/science/article/pii/S2352396423001536UK BiobankHLA heterozygosityHLA evolutionary DivergenceCancer susceptibility |
| spellingShingle | Qiao-Ling Wang Tong-Min Wang Chang-Mi Deng Wen-Li Zhang Yong-Qiao He Wen-Qiong Xue Ying Liao Da-Wei Yang Mei-Qi Zheng Wei-Hua Jia Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context EBioMedicine UK Biobank HLA heterozygosity HLA evolutionary Divergence Cancer susceptibility |
| title | Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context |
| title_full | Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context |
| title_fullStr | Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context |
| title_full_unstemmed | Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context |
| title_short | Association of HLA diversity with the risk of 25 cancers in the UK BiobankResearch in context |
| title_sort | association of hla diversity with the risk of 25 cancers in the uk biobankresearch in context |
| topic | UK Biobank HLA heterozygosity HLA evolutionary Divergence Cancer susceptibility |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423001536 |
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