Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility
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Published:2023-06-06
Issue:6
Volume:11
Page:1648
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ISSN:2227-9059
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Container-title:Biomedicines
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language:en
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Short-container-title:Biomedicines
Author:
Tsai Chia-Wen12, Shih Liang-Chun123ORCID, Chang Wen-Shin12, Hsu Che-Lun3, He Jie-Long4, Hsia Te-Chun2, Wang Yun-Chi12, Gu Jian5, Bau Da-Tian126ORCID
Affiliation:
1. Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404333, Taiwan 2. Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung 404332, Taiwan 3. Department of Otorhinolaryngology, China Medical University Hospital, Taichung 404332, Taiwan 4. Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung 413305, Taiwan 5. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 6. Department of Bioinformatics and Medical Engineering, Asia University, Taichung 413305, Taiwan
Abstract
Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.
Funder
Asia University and China Medical University
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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